Staphylococcus aureus

In 1880, Alexander Ogston, a Scottish surgeon, discovered that Staphylococcus can cause wound infections after noticing groups of bacteria in pus from a surgical abscess during a procedure he was performing. He named it Staphylococcus after its clustered appearance evident under a microscope. Then, in 1884, German scientist Friedrich Julius Rosenbach identified Staphylococcus aureus, discriminating and separating it from Staphylococcus albus, a related bacterium. In the early 1930s, doctors began to use a more streamlined test to detect the presence of an S. aureus infection by the means of coagulase testing, which enables detection of an enzyme produced by the bacterium. Prior to the 1940s, S. aureus infections were fatal in the majority of patients. However, doctors discovered that the use of penicillin could cure S. aureus infections. Unfortunately, by the end of the 1940s, penicillin resistance became widespread amongst this bacterium population and outbreaks of the resistant strain began to occur.{{cite journal| vauthors = Orent W |date=2006|title=A Brief History of Staph|journal=Proto Magazine}}

Staphylococcus aureus can be sorted into ten dominant human lineages.{{Cite web |title=S. aureus clonal complex designation |url=https://pubmlst.org/organisms/staphylococcus-aureus/clonal-complexes |access-date=2024-02-28 |website=PubMLST |language=en}} There are numerous minor lineages as well, but these are not seen in the population as often. Genomes of bacteria within the same lineage are mostly conserved, with the exception of mobile genetic elements. Mobile genetic elements that are common in S. aureus include bacteriophages, pathogenicity islands, plasmids, transposons, and staphylococcal cassette chromosomes. These elements have enabled S. aureus to continually evolve and gain new traits. There is a great deal of genetic variation within the S. aureus species. A study by Fitzgerald et al. (2001) revealed that approximately 22% of the S. aureus genome is non-coding and thus can differ from bacterium to bacterium. An example of this difference is seen in the species' virulence. Only a few strains of S. aureus are associated with infections in humans. This demonstrates that there is a large range of infectious ability within the species.{{cite journal | vauthors = Fitzgerald JR, Sturdevant DE, Mackie SM, Gill SR, Musser JM | title = Evolutionary genomics of Staphylococcus aureus: insights into the origin of methicillin-resistant strains and the toxic shock syndrome epidemic | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 98 | issue = 15 | pages = 8821–6 | date = July 2001 | pmid = 11447287 | pmc = 37519 | doi = 10.1073/pnas.161098098 | doi-access = free | bibcode = 2001PNAS...98.8821F }}

It has been proposed that one possible reason for the great deal of heterogeneity within the species could be due to its reliance on heterogeneous infections. This occurs when multiple different types of S. aureus cause an infection within a host. The different strains can secrete different enzymes or bring different antibiotic resistances to the group, increasing its pathogenic ability.{{cite journal | vauthors = Lindsay JA | title = Genomic variation and evolution of Staphylococcus aureus | journal = International Journal of Medical Microbiology | volume = 300 | issue = 2–3 | pages = 98–103 | date = February 2010 | pmid = 19811948 | doi = 10.1016/j.ijmm.2009.08.013 }} Thus, there is a need for a large number of mutations and acquisitions of mobile genetic elements.{{citation needed|date=December 2022}}

Another notable evolutionary process within the S. aureus species is its co-evolution with its human hosts. Over time, this parasitic relationship has led to the bacterium's ability to be carried in the nasopharynx of humans without causing symptoms or infection. This allows it to be passed throughout the human population, increasing its fitness as a species.{{cite journal | vauthors = Fitzgerald JR | title = Evolution of Staphylococcus aureus during human colonization and infection | journal = Infection, Genetics and Evolution | volume = 21 | pages = 542–7 | date = January 2014 | pmid = 23624187 | doi = 10.1016/j.meegid.2013.04.020 | bibcode = 2014InfGE..21..542F }} However, only approximately 50% of the human population are carriers of S. aureus, with 20% as continuous carriers and 30% as intermittent. This leads scientists to believe that there are many factors that determine whether S. aureus is carried asymptomatically in humans, including factors that are specific to an individual person. According to a 1995 study by Hofman et al., these factors may include age, sex, diabetes, and smoking. They also determined some genetic variations in humans that lead to an increased ability for S. aureus to colonize, notably a polymorphism in the glucocorticoid receptor gene that results in larger corticosteroid production. In conclusion, there is evidence that any strain of this bacterium can become invasive, as this is highly dependent upon human factors.{{cite journal | vauthors = van Belkum A, Melles DC, Nouwen J, van Leeuwen WB, van Wamel W, Vos MC, Wertheim HF, Verbrugh HA | title = Co-evolutionary aspects of human colonisation and infection by Staphylococcus aureus | journal = Infection, Genetics and Evolution | volume = 9 | issue = 1 | pages = 32–47 | date = January 2009 | pmid = 19000784 | doi = 10.1016/j.meegid.2008.09.012 | bibcode = 2009InfGE...9...32V }}

Though S. aureus has quick reproductive and micro-evolutionary rates, there are multiple barriers that prevent evolution with the species. One such barrier is AGR, which is a global accessory gene regulator within the bacteria. This such regulator has been linked to the virulence level of the bacteria. Loss of function mutations within this gene have been found to increase the fitness of the bacterium containing it. Thus, S. aureus must make a trade-off to increase their success as a species, exchanging reduced virulence for increased drug resistance. Another barrier to evolution is the Sau1 Type I restriction modification (RM) system. This system exists to protect the bacterium from foreign DNA by digesting it. Exchange of DNA between the same lineage is not blocked, since they have the same enzymes and the RM system does not recognize the new DNA as foreign, but transfer between different lineages is blocked.

Image:Staphylococcus aureus Gram.jpg cells, which typically occur in clusters: The cell wall readily absorbs the crystal violet stain.]]

File:Staphylococcus aureus biochemical tests for identification.jpg

Staphylococcus aureus ({{IPAc-en|ˌ|s|t|æ|f|ᵻ|l|ə|ˈ|k|ɒ|k|ə|s|_|ˈ|ɔːr|i|ə|s|,_|-|l|oʊ|-}},{{refn|{{Dictionary.com|Staphylococcus}} {{Dictionary.com|aureus}}}}{{refn|{{cite web |url=https://www.oxforddictionaries.com/definition/english/staphylococcus |archive-url=https://web.archive.org/web/20120818053533/http://oxforddictionaries.com/definition/english/staphylococcus |url-status=dead |archive-date=18 August 2012 |title=staphylococcus – definition of staphylococcus in English from the Oxford dictionary |publisher=OxfordDictionaries.com |access-date=20 January 2016 }} {{cite web |url=https://www.oxforddictionaries.com/definition/english/aureus |archive-url=https://web.archive.org/web/20120716032155/http://oxforddictionaries.com/definition/english/aureus |url-status=dead |archive-date=16 July 2012 |title=aureus – definition of aureus in English from the Oxford dictionary |publisher=OxfordDictionaries.com |access-date=20 January 2016 }}}} Greek {{Lang|grc|σταφυλόκοκκος}} {{Gloss|grape-cluster berry}}, Latin {{Lang|la|aureus}}, {{Gloss|golden}}) is a facultative anaerobic, Gram-positive coccal (round) bacterium also known as "golden staph" and "oro staphira". S. aureus is nonmotile and does not form spores."Pathogen Safety Data Sheet – Infectious Substances." Staphylococcus cells have a diameter of 0.7–1.2 um. Staphylococcus Aureus. Public Health Agency of Canada, 2011. Web In medical literature, the bacterium is often referred to as S. aureus, Staph aureus or Staph a..{{cite web|url=https://www.ccohs.ca/oshanswers/biol_hazards/methicillin.html|title= Canadian Centre for Occupational Health and Safety |access-date=8 April 2016}} S. aureus appears as staphylococci (grape-like clusters) when viewed through a microscope, and has large, round, golden-yellow colonies, often with hemolysis, when grown on blood agar plates.{{cite book | veditors = Ryan KJ, Ray CG | title = Sherris Medical Microbiology | edition = 4th | publisher = McGraw Hill | year = 2004 | isbn= 978-0-8385-8529-0 }} S. aureus reproduces asexually by binary fission. Complete separation of the daughter cells is mediated by S. aureus autolysin, and in its absence or targeted inhibition, the daughter cells remain attached to one another and appear as clusters.{{cite journal | vauthors = Varrone JJ, de Mesy Bentley KL, Bello-Irizarry SN, Nishitani K, Mack S, Hunter JG, Kates SL, Daiss JL, Schwarz EM | title = Passive immunization with anti-glucosaminidase monoclonal antibodies protects mice from implant-associated osteomyelitis by mediating opsonophagocytosis of Staphylococcus aureus megaclusters | journal = Journal of Orthopaedic Research | volume = 32 | issue = 10 | pages = 1389–96 | date = October 2014 | pmid = 24992290 | pmc = 4234088 | doi = 10.1002/jor.22672 }}

Staphylococcus aureus is catalase-positive (meaning it can produce the enzyme catalase). Catalase converts hydrogen peroxide ({{chem|H|2|O|2}}) to water and oxygen. Catalase-activity tests are sometimes used to distinguish staphylococci from enterococci and streptococci. Previously, S. aureus was differentiated from other staphylococci by the coagulase test. However, not all S. aureus strains are coagulase-positivePreTest, Surgery, 12th ed., p.88 and incorrect species identification can impact effective treatment and control measures.{{cite journal | vauthors = Matthews KR, Roberson J, Gillespie BE, Luther DA, Oliver SP | title = Identification and Differentiation of Coagulase-Negative Staphylococcus aureus by Polymerase Chain Reaction | journal = Journal of Food Protection | volume = 60 | issue = 6 | pages = 686–8 | date = June 1997 | pmid = 31195568 | doi = 10.4315/0362-028X-60.6.686 | doi-access = free }}

Natural genetic transformation is a reproductive process involving DNA transfer from one bacterium to another through the intervening medium, and the integration of the donor sequence into the recipient genome by homologous recombination. S. aureus was found to be capable of natural genetic transformation, but only at low frequency under the experimental conditions employed.{{cite journal | vauthors = Morikawa K, Takemura AJ, Inose Y, Tsai M, Nguyen TL, Ohta T, Msadek T | title = Expression of a cryptic secondary sigma factor gene unveils natural competence for DNA transformation in Staphylococcus aureus | journal = PLOS Pathogens | volume = 8 | issue = 11 | pages = e1003003 | year = 2012 | pmid = 23133387 | pmc = 3486894 | doi = 10.1371/journal.ppat.1003003 | doi-access = free }} Further studies suggested that the development of competence for natural genetic transformation may be substantially higher under appropriate conditions, yet to be discovered.{{cite journal | vauthors = Fagerlund A, Granum PE, Håvarstein LS | title = Staphylococcus aureus competence genes: mapping of the SigH, ComK1 and ComK2 regulons by transcriptome sequencing | journal = Molecular Microbiology | volume = 94 | issue = 3 | pages = 557–579 | date = November 2014 | pmid = 25155269 | doi = 10.1111/mmi.12767 | s2cid = 1568023 | doi-access = free }}

In humans, S. aureus can be present in the upper respiratory tract, gut mucosa, and skin as a member of the normal microbiota.{{cite journal | vauthors = Schenck LP, Surette MG, Bowdish DM | title = Composition and immunological significance of the upper respiratory tract microbiota | journal = FEBS Letters | volume = 590 | issue = 21 | pages = 3705–20 | date = November 2016 | pmid = 27730630 | pmc = 7164007 | doi = 10.1002/1873-3468.12455 }}{{cite journal | vauthors = Wollina U | title = Microbiome in atopic dermatitis | journal = Clinical, Cosmetic and Investigational Dermatology | volume = 10 | pages = 51–56 | date = 2017 | pmid = 28260936 | pmc = 5327846 | doi = 10.2147/CCID.S130013 | doi-access = free }}{{cite journal | vauthors = Otto M | title = Staphylococcus colonization of the skin and antimicrobial peptides | journal = Expert Review of Dermatology | volume = 5 | issue = 2 | pages = 183–195 | date = April 2010 | pmid = 20473345 | pmc = 2867359 | doi = 10.1586/edm.10.6 }} However, because S. aureus can cause disease under certain host and environmental conditions, it is characterized as a pathobiont.

In the United States, MRSA infections alone are estimated to cost the healthcare system over $3.2 billion annually{{Cite journal |last1=Roberts |first1=Rebecca R. |last2=Hota |first2=Bala |last3=Ahmad |first3=Ibrar |last4=Scott |first4=R. Douglas, II |last5=Foster |first5=Susan D. |last6=Abbasi |first6=Fauzia |last7=Schabowski |first7=Shari |last8=Kampe |first8=Linda M. |last9=Ciavarella |first9=Ginevra G. |last10=Supino |first10=Mark |last11=Naples |first11=Jeremy |last12=Cordell |first12=Ralph |last13=Levy |first13=Stuart B. |last14=Weinstein |first14=Robert A. |date=2009-10-15 |title=Hospital and Societal Costs of Antimicrobial-Resistant Infections in a Chicago Teaching Hospital: Implications for Antibiotic Stewardship |url=https://academic.oup.com/cid/article-abstract/49/8/1175/425330?redirectedFrom=fulltext |journal=Clinical Infectious Diseases |volume=49 |issue=8 |pages=1175–1184 |doi=10.1086/605630 |pmid=19739972 |issn=1058-4838}}. These infections account for nearly 20,000 deaths each year in the U.S., exceeding those caused by HIV/AIDS, Parkinson's disease, and homicide{{Cite journal |last1=Klevens |first1=R. Monina |last2=Morrison |first2=Melissa A. |last3=Nadle |first3=Joelle |last4=Petit |first4=Susan |last5=Gershman |first5=Ken |last6=Ray |first6=Susan |last7=Harrison |first7=Lee H. |last8=Lynfield |first8=Ruth |last9=Dumyati |first9=Ghinwa |last10=Townes |first10=John M. |last11=Craig |first11=Allen S. |last12=Zell |first12=Elizabeth R. |last13=Fosheim |first13=Gregory E. |last14=McDougal |first14=Linda K. |last15=Carey |first15=Roberta B. |date=2007-10-17 |title=Invasive Methicillin-Resistant Staphylococcus aureus Infections in the United States |url=https://jamanetwork.com/journals/jama/fullarticle/209197 |journal=JAMA |volume=298 |issue=15 |pages=1763–1771 |doi=10.1001/jama.298.15.1763 |pmid=17940231 |issn=0098-7484}}. Annually, over 119,000 bloodstream infections in the U.S. are attributed to S. aureus{{Cite web |date=2020-12-10 |title=Staphylococcus aureus in Healthcare Settings |url=https://www.cdc.gov/hai/organisms/staph.html |archive-url=http://web.archive.org/web/20240515064151/https://www.cdc.gov/HAI/organisms/staph.html |archive-date=2024-05-15 |access-date=2025-04-28 |website=www.cdc.gov |language=en-us}}. S. aureus infections are ranked as one of the costliest healthcare-associated infections (HAIs), with each case averaging $23,000 to $46,000 in treatment and hospital resource utilization{{Cite journal |last1=Zimlichman |first1=Eyal |last2=Henderson |first2=Daniel |last3=Tamir |first3=Orly |last4=Franz |first4=Calvin |last5=Song |first5=Peter |last6=Yamin |first6=Cyrus K. |last7=Keohane |first7=Carol |last8=Denham |first8=Charles R. |last9=Bates |first9=David W. |date=2013-12-09 |title=Health Care–Associated Infections: A Meta-analysis of Costs and Financial Impact on the US Health Care System |url=https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/1733452 |journal=JAMA Internal Medicine |volume=173 |issue=22 |pages=2039–2046 |doi=10.1001/jamainternmed.2013.9763 |pmid=23999949 |issn=2168-6106}}.

On average, patients with MRSA infections experience a lengthened hospital stay of approximately 6 to 11 days, which drives up inpatient care costs{{Cite journal |last1=Cohen |first1=Stuart H. |last2=Gerding |first2=Dale N. |last3=Johnson |first3=Stuart |last4=Kelly |first4=Ciaran P. |last5=Loo |first5=Vivian G. |last6=McDonald |first6=L. Clifford |last7=Pepin |first7=Jacques |last8=Wilcox |first8=Mark H. |date=May 2010 |title=Clinical Practice Guidelines for Clostridium difficile Infection in Adults: 2010 Update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA) |url=https://www.cambridge.org/core/journals/infection-control-and-hospital-epidemiology/article/abs/clinical-practice-guidelines-for-clostridium-difficile-infection-in-adults-2010-update-by-the-society-for-healthcare-epidemiology-of-america-shea-and-the-infectious-diseases-society-of-america-idsa/F15EC65473C368F9E24434B46B17B19A |journal=Infection Control & Hospital Epidemiology |language=en |volume=31 |issue=5 |pages=431–455 |doi=10.1086/651706 |pmid=20307191 |issn=0899-823X}}{{Cite journal |last=Kourtis |first=Athena P. |date=2019 |title=Vital Signs: Epidemiology and Recent Trends in Methicillin-Resistant and in Methicillin-Susceptible Staphylococcus aureus Bloodstream Infections — United States |url=https://www.cdc.gov/mmwr/volumes/68/wr/mm6809e1.htm?s_cid=mm6809e1_w |journal=MMWR. Morbidity and Mortality Weekly Report |language=en-us |volume=68 |issue=9 |pages=214–219 |doi=10.15585/mmwr.mm6809e1 |issn=0149-2195 |pmc=6421967 |pmid=30845118}}. The burden extends beyond direct healthcare expenses. Indirect costs, such as lost wages, reduced productivity, and long-term disability, can significantly amplify the overall economic toll. Severe S. aureus infections, including bacteremia, endocarditis, and osteomyelitis, often require prolonged recovery and rehabilitation, affecting patients' ability to return to work or perform daily activities{{Cite journal |last1=Cosgrove |first1=Sara E. |last2=Sakoulas |first2=George |last3=Perencevich |first3=Eli N. |last4=Schwaber |first4=Mitchell J. |last5=Karchmer |first5=Adolf W. |last6=Carmeli |first6=Yehuda |date=2003-01-01 |title=Comparison of Mortality Associated with Methicillin-Resistant and Methicillin-Susceptible Staphylococcus aureus Bacteremia: A Meta-analysis |url=https://academic.oup.com/cid/article-abstract/36/1/53/283567?redirectedFrom=fulltext |journal=Clinical Infectious Diseases |volume=36 |issue=1 |pages=53–59 |doi=10.1086/345476 |issn=1058-4838}}.

Hospitals also invest heavily in infection control protocols to limit the spread of S. aureus, especially drug-resistant strains. These measures include routine screening, isolation practices, use of personal protective equipment, and antibiotic stewardship programs, which collectively contribute to rising operational costs. These necessary preventative measures can raise hospital costs by tens of thousands of dollars{{Cite journal |last1=Dantes |first1=Raymund |last2=Mu |first2=Yi |last3=Belflower |first3=Ruth |last4=Aragon |first4=Deborah |last5=Dumyati |first5=Ghinwa |last6=Harrison |first6=Lee H. |last7=Lessa |first7=Fernanda C. |last8=Lynfield |first8=Ruth |last9=Nadle |first9=Joelle |last10=Petit |first10=Susan |last11=Ray |first11=Susan M. |last12=Schaffner |first12=William |last13=Townes |first13=John |last14=Fridkin |first14=Scott |last15=for the Emerging Infections Program–Active Bacterial Core Surveillance MRSA Surveillance Investigators |date=2013-11-25 |title=National Burden of Invasive Methicillin-Resistant Staphylococcus aureus Infections, United States, 2011 |journal=JAMA Internal Medicine |volume=173 |issue=21 |pages=1970–1978 |doi=10.1001/jamainternmed.2013.10423 |issn=2168-6106 |pmc=10887428 |pmid=24043270}}.

{{Further|Coagulase-positive staphylococcal infection}}

File:3D Medical Animation Staphylococcus Aureus.jpg

Image:MRSA7820.jpg (SEM) depicts numerous clumps of methicillin-resistant S. aureus (MRSA) bacteria.]]

While S. aureus usually acts as a commensal bacterium, asymptomatically colonizing about 30% of the human population, it can sometimes cause disease.{{cite journal | vauthors = Tong SY, Davis JS, Eichenberger E, Holland TL, Fowler VG | title = Staphylococcus aureus infections: epidemiology, pathophysiology, clinical manifestations, and management | journal = Clinical Microbiology Reviews | volume = 28 | issue = 3 | pages = 603–661 | date = July 2015 | pmid = 26016486 | pmc = 4451395 | doi = 10.1128/CMR.00134-14 }} In particular, S. aureus is one of the most common causes of bacteremia and infective endocarditis. Additionally, it can cause various skin and soft-tissue infections, particularly when skin or mucosal barriers have been breached.

Staphylococcus aureus infections can spread through contact with pus from an infected wound, skin-to-skin contact with an infected person, and contact with objects used by an infected person such as towels, sheets, clothing, or athletic equipment. Joint replacements put a person at particular risk of septic arthritis, staphylococcal endocarditis (infection of the heart valves), and pneumonia.{{cite journal | vauthors = Kuehnert MJ, Hill HA, Kupronis BA, Tokars JI, Solomon SL, Jernigan DB | title = Methicillin-resistant-Staphylococcus aureus hospitalizations, United States | journal = Emerging Infectious Diseases | volume = 11 | issue = 6 | pages = 868–872 | date = June 2005 | pmid = 15963281 | pmc = 3367609 | doi = 10.3201/eid1106.040831 }}

Staphylococcus aureus is a significant cause of chronic biofilm infections on medical implants, and the repressor of toxins is part of the infection pathway.{{cite journal | vauthors = Kavanaugh JS, Horswill AR | title = Impact of Environmental Cues on Staphylococcal Quorum Sensing and Biofilm Development | journal = The Journal of Biological Chemistry | volume = 291 | issue = 24 | pages = 12556–64 | date = June 2016 | pmid = 27129223 | pmc = 4933443 | doi = 10.1074/jbc.R116.722710 | type = Review | doi-access = free }}

Staphylococcus aureus can lie dormant in the body for years undetected. Once symptoms begin to show, the host is contagious for another two weeks, and the overall illness lasts a few weeks. If untreated, though, the disease can be deadly.{{cite web|url=https://www.cdc.gov/hai/organisms/staph.html|title=Staphylococcus aureus in Healthcare Settings {{!}} HAI|website=CDC|access-date=19 April 2017}} Deeply penetrating S. aureus infections can be severe.{{citation needed|date=December 2022}}

Skin infections are the most common form of S. aureus infection. This can manifest in various ways, including small benign boils, folliculitis, impetigo, cellulitis, and more severe, invasive soft-tissue infections.

Staphylococcus aureus is extremely prevalent in persons with atopic dermatitis (AD), more commonly known as eczema.{{cite journal | vauthors = Monnot GC, Wegrecki M, Cheng TY, Chen YL, Sallee BN, Chakravarthy R, Karantza IM, Tin SY, Khaleel AE, Monga I, Uwakwe LN, Tillman A, Cheng B, Youssef S, Ng SW, Shahine A, Garcia-Vilas JA, Uhlemann AC, Bordone LA, Han A, Rohde CH, Ogg G, Moody DB, Rossjohn J, de Jong A| title = Staphylococcal phosphatidylglycerol antigens activate human T cells via CD1a | journal = Nature Immunology | volume = 24 | issue = 1 | pages = 110–122 | date = January 2023 | pmid = 35265979 | doi = 10.1038/s41590-022-01375-z| s2cid = 255039948 | pmc = 10389259 }} It is mostly found in fertile, active places, including the armpits, hair, and scalp. Large pimples that appear in those areas may exacerbate the infection if lacerated. Colonization of S. aureus drives inflammation of AD.{{cite journal |vauthors=Kobayashi T, Glatz M, Horiuchi K, Kawasaki H, Akiyama H, Kaplan DH, Kong HH, Amagai M, Nagao K |date=April 2015 |title=Dysbiosis and Staphylococcus aureus Colonization Drives Inflammation in Atopic Dermatitis |journal=Immunity |volume=42 |issue=4 |pages=756–766 |doi=10.1016/j.immuni.2015.03.014 |pmc=4407815 |pmid=25902485}} S. aureus is believed to exploit defects in the skin barrier of persons with atopic dermatitis, triggering cytokine expression and therefore exacerbating symptoms.{{cite journal |vauthors=Nakatsuji T, Chen TH, Two AM, Chun KA, Narala S, Geha RS, Hata TR, Gallo RL |date=November 2016 |title=Staphylococcus aureus Exploits Epidermal Barrier Defects in Atopic Dermatitis to Trigger Cytokine Expression |journal=The Journal of Investigative Dermatology |volume=136 |issue=11 |pages=2192–2200 |doi=10.1016/j.jid.2016.05.127 |pmc=5103312 |pmid=27381887}} This can lead to staphylococcal scalded skin syndrome, a severe form of which can be seen in newborns.{{cite journal | vauthors = Curran JP, Al-Salihi FL | title = Neonatal staphylococcal scalded skin syndrome: massive outbreak due to an unusual phage type | journal = Pediatrics | volume = 66 | issue = 2 | pages = 285–290 | date = August 1980 | pmid = 6447271 | doi = 10.1542/peds.66.2.285 | s2cid = 21783186 }}

The role of S. aureus in causing itching in atopic dermatitis has been studied.{{Cite journal |last1=Gallo |first1=Richard L. |last2=Horswill |first2=Alexander R. |date=May 2024 |title=Staphylococcus aureus: The Bug Behind the Itch in Atopic Dermatitis |journal=Journal of Investigative Dermatology |volume=144 |issue=5 |pages=950–953 |doi=10.1016/j.jid.2024.01.001|pmid=38430083 |doi-access=free }}

Antibiotics are commonly used to target overgrowth of S. aureus but their benefit is limited and they increase the risk of antimicrobial resistance. For these reasons, they are only recommended for people who not only present symptoms on the skin but feel systematically unwell.{{cite journal | vauthors = George SM, Karanovic S, Harrison DA, Rani A, Birnie AJ, Bath-Hextall FJ, Ravenscroft JC, Williams HC | title = Interventions to reduce Staphylococcus aureus in the management of eczema | journal = The Cochrane Database of Systematic Reviews | volume = 2019 | issue = 10 | date = October 2019 | pmid = 31684694 | pmc = 6818407 | doi = 10.1002/14651858.CD003871.pub3 }}{{Cite report |url=https://evidence.nihr.ac.uk/collection/eczema-in-children-uncertainties-addressed/ |title=Eczema in children: uncertainties addressed |date=2024-03-19 |publisher=NIHR Evidence |doi=10.3310/nihrevidence_62438 |language=en}}{{Cite web |date=2021-03-02 |title=Secondary bacterial infection of eczema and other common skin conditions: antimicrobial prescribing. NICE guideline [NG190] |url=https://www.nice.org.uk/guidance/ng190/chapter/Recommendations |access-date=2024-07-26 |website=National Institute for Health and Care Excellence}}

Staphylococcus aureus is also responsible for food poisoning and achieves this by generating toxins in the food, which is then ingested.{{cite web |url= https://www.cdc.gov/foodsafety/diseases/staphylococcal.html |title= Staphylococcal Food Poisoning |date=4 October 2016|website=cdc.gov |publisher=hhs.gov |access-date= 23 October 2016}} Its incubation period lasts 30 minutes to eight hours,"Staphylococcus." Foodsafety.gov, U.S. Department of Health and Human Services, https://www.foodsafety.gov/poisoning/causes/bacteriaviruses/staphylococcus/. with the illness itself lasting from 30 minutes to 3 days."Staphylococcal Food Poisoning." Food Safety, Centers for Disease Control and Prevention, 4 October 2016, https://www.cdc.gov/foodsafety/diseases/staphylococcal.html. Preventive measures one can take to help prevent the spread of the disease include washing hands thoroughly with soap and water before preparing food. The Centers for Disease Control and Prevention recommends staying away from any food if ill, and wearing gloves if any open wounds occur on hands or wrists while preparing food. If storing food for longer than 2 hours, it is recommended to keep the food below 4.4 or above 60 °C (below 40 or above 140 °F).{{cite web | vauthors = Woodson J |title=Centers for disease control and prevention |url= https://www.cdc.gov/foodsafety/diseases/staphylococcal.html |archive-url= https://web.archive.org/web/20160208065403/http://www.cdc.gov/foodsafety/diseases/staphylococcal.html |url-status=live |archive-date=8 February 2016 |website=Food Safety |access-date=24 October 2017 }}

Staphylococcus aureus is a common cause of major bone and joint infections, including osteomyelitis, septic arthritis, and infections following joint replacement surgeries.{{cite journal |vauthors=Latha T, Anil B, Manjunatha H, Chiranjay M, Elsa D, Baby N, Anice G |title=MRSA: the leading pathogen of orthopedic infection in a tertiary care hospital, South India |journal=Afr Health Sci |volume=19 |issue=1 |pages=1393–1401 |date=March 2019 |pmid=31148966 |pmc=6531934 |doi=10.4314/ahs.v19i1.12 }}

Staphylococcus aureus is a leading cause of bloodstream infections throughout much of the industrialized world.{{cite journal | vauthors = Rasmussen RV, Fowler VG, Skov R, Bruun NE | title = Future challenges and treatment of Staphylococcus aureus bacteremia with emphasis on MRSA | journal = Future Microbiology | volume = 6 | issue = 1 | pages = 43–56 | date = January 2011 | pmid = 21162635 | pmc = 3031962 | doi = 10.2217/fmb.10.155 }} Infection is generally associated with breaks in the skin or mucosal membranes due to surgery, injury, or use of intravascular devices such as cannulas, hemodialysis machines, or hypodermic needles. Once the bacteria have entered the bloodstream, they can infect various organs, causing infective endocarditis, septic arthritis, and osteomyelitis. This disease is particularly prevalent and severe in the very young and very old.

Without antibiotic treatment, S. aureus bacteremia has a case fatality rate around 80%. With antibiotic treatment, case fatality rates range from 15% to 50% depending on the age and health of the patient, as well as the antibiotic resistance of the S. aureus strain.

Staphylococcus aureus is often found in biofilms formed on medical devices implanted in the body or on human tissue. It is commonly found with another pathogen, Candida albicans, forming multispecies biofilms. The latter is suspected to help S. aureus penetrate human tissue. A higher mortality is linked with multispecies biofilms.{{cite journal | vauthors = Zago CE, Silva S, Sanitá PV, Barbugli PA, Dias CM, Lordello VB, Vergani CE | title = Dynamics of biofilm formation and the interaction between Candida albicans and methicillin-susceptible (MSSA) and -resistant Staphylococcus aureus (MRSA) | journal = PLOS ONE | volume = 10 | issue = 4 | pages = e0123206 | year = 2015 | pmid = 25875834 | pmc = 4395328 | doi = 10.1371/journal.pone.0123206 | doi-access = free | bibcode = 2015PLoSO..1023206Z }}

Staphylococcus aureus biofilm is the predominant cause of orthopedic implant-related infections, but is also found on cardiac implants, vascular grafts, various catheters, and cosmetic surgical implants.{{cite journal | vauthors = Nandakumar V, Chittaranjan S, Kurian VM, Doble M | date = 2013 | title = Characteristics of bacterial biofilm associated with implant material in clinical practice |journal=Polymer Journal|volume=45|issue=2|pages=137–152|doi=10.1038/pj.2012.130 | doi-access = free }}{{cite journal | vauthors = Archer NK, Mazaitis MJ, Costerton JW, Leid JG, Powers ME, Shirtliff ME | title = Staphylococcus aureus biofilms: properties, regulation, and roles in human disease | journal = Virulence | volume = 2 | issue = 5 | pages = 445–459 | date = 1 September 2011 | pmid = 21921685 | pmc = 3322633 | doi = 10.4161/viru.2.5.17724 }} After implantation, the surface of these devices becomes coated with host proteins, which provide a rich surface for bacterial attachment and biofilm formation. Once the device becomes infected, it must be completely removed, since S. aureus biofilm cannot be destroyed by antibiotic treatments.

Current therapy for S. aureus biofilm-mediated infections involves surgical removal of the infected device followed by antibiotic treatment. Conventional antibiotic treatment alone is not effective in eradicating such infections. An alternative to postsurgical antibiotic treatment is using antibiotic-loaded, dissolvable calcium sulfate beads, which are implanted with the medical device. These beads can release high doses of antibiotics at the desired site to prevent the initial infection.

Novel treatments for S. aureus biofilm involving nano silver particles, bacteriophages, and plant-derived antibiotic agents are being studied. These agents have shown inhibitory effects against S. aureus embedded in biofilms.{{cite journal | vauthors = Chung PY, Toh YS | title = Anti-biofilm agents: recent breakthrough against multi-drug resistant Staphylococcus aureus | journal = Pathogens and Disease | volume = 70 | issue = 3 | pages = 231–9 | date = April 2014 | pmid = 24453168 | doi = 10.1111/2049-632x.12141 | doi-access = free }} A class of enzymes have been found to have biofilm matrix-degrading ability, thus may be used as biofilm dispersal agents in combination with antibiotics.{{cite journal | vauthors = Hogan S, Zapotoczna M, Stevens NT, Humphreys H, O'Gara JP, O'Neill E | title = Potential use of targeted enzymatic agents in the treatment of Staphylococcus aureus biofilm-related infections | journal = The Journal of Hospital Infection | volume = 96 | issue = 2 | pages = 177–182 | date = June 2017 | pmid = 28351512 | doi = 10.1016/j.jhin.2017.02.008 }}

Staphylococcus aureus can survive on dogs,{{cite journal | vauthors = Boost MV, O'Donoghue MM, James A | title = Prevalence of Staphylococcus aureus carriage among dogs and their owners | journal = Epidemiology and Infection | volume = 136 | issue = 7 | pages = 953–964 | date = July 2008 | pmid = 17678561 | pmc = 2870875 | doi = 10.1017/S0950268807009326 }} cats,{{cite journal | vauthors = Hanselman BA, Kruth SA, Rousseau J, Weese JS | title = Coagulase positive staphylococcal colonization of humans and their household pets | journal = The Canadian Veterinary Journal | volume = 50 | issue = 9 | pages = 954–8 | date = September 2009 | pmid = 19949556 | pmc = 2726022 }} and horses,{{cite journal | vauthors = Burton S, Reid-Smith R, McClure JT, Weese JS | title = Staphylococcus aureus colonization in healthy horses in Atlantic Canada | journal = The Canadian Veterinary Journal | volume = 49 | issue = 8 | pages = 797–9 | date = August 2008 | pmid = 18978975 | pmc = 2465786 }} and can cause bumblefoot in chickens.{{cite web |title=Staphylococcosis, Staphylococcal Arthritis, Bumble Foot |publisher=The Poultry Site |url=http://www.thepoultrysite.com/diseaseinfo/143/staphylococcosis-staphylococcal-arthritis-bumble-foot |access-date=22 October 2013}} Some believe health-care workers' dogs should be considered a significant source of antibiotic-resistant S. aureus, especially in times of outbreak. In a 2008 study by Boost, O'Donoghue, and James, it was found that just about 90% of S. aureus colonized within pet dogs presented as resistant to at least one antibiotic. The nasal region has been implicated as the most important site of transfer between dogs and humans.{{cite journal | vauthors = Boost MV, O'Donoghue MM, James A | title = Prevalence of Staphylococcus aureus carriage among dogs and their owners | journal = Epidemiology and Infection | volume = 136 | issue = 7 | pages = 953–964 | date = July 2008 | pmid = 17678561 | pmc = 2870875 | doi = 10.1017/s0950268807009326 | hdl = 10397/7558 }}

Staphylococcus aureus is one of the causal agents of mastitis in dairy cows. Its large polysaccharide capsule protects the organism from recognition by the cow's immune defenses.{{cite journal | vauthors = Cenci-Goga BT, Karama M, Rossitto PV, Morgante RA, Cullor JS | title = Enterotoxin production by Staphylococcus aureus isolated from mastitic cows | journal = Journal of Food Protection | volume = 66 | issue = 9 | pages = 1693–6 | date = September 2003 | pmid = 14503727 | doi = 10.4315/0362-028X-66.9.1693 | doi-access = free | url = http://meridian.allenpress.com/jfp/article-pdf/66/9/1693/1676680/0362-028x-66_9_1693.pdf }}

{{Main|Virulence factor}}

Staphylococcus aureus produces various enzymes such as coagulase (bound and free coagulases) which facilitates the conversion of fibrinogen to fibrin to cause clots which is important in skin infections.{{cite journal | vauthors = Cheung GY, Bae JS, Otto M | title = Pathogenicity and virulence of Staphylococcus aureus | journal = Virulence | volume = 12 | issue = 1 | pages = 547–569 | date = December 2021 | pmid = 33522395 | pmc = 7872022 | doi = 10.1080/21505594.2021.1878688 }} Hyaluronidase (also known as spreading factor) breaks down hyaluronic acid and helps in spreading it. Deoxyribonuclease, which breaks down the DNA, protects S. aureus from neutrophil extracellular trap-mediated killing.{{cite journal | vauthors = Berends ET, Horswill AR, Haste NM, Monestier M, Nizet V, von Köckritz-Blickwede M | title = Nuclease expression by Staphylococcus aureus facilitates escape from neutrophil extracellular traps | language = english | journal = Journal of Innate Immunity | volume = 2 | issue = 6 | pages = 576–586 | date = 2010 | pmid = 20829609 | pmc = 2982853 | doi = 10.1159/000319909 }}{{cite journal | vauthors = Monteith AJ, Miller JM, Maxwell CN, Chazin WJ, Skaar EP | title = Neutrophil extracellular traps enhance macrophage killing of bacterial pathogens | language = EN | journal = Science Advances | volume = 7 | issue = 37 | pages = eabj2101 | date = September 2021 | pmid = 34516771 | pmc = 8442908 | doi = 10.1126/sciadv.abj2101 | bibcode = 2021SciA....7.2101M | doi-access = free }} S. aureus also produces lipase to digest lipids, staphylokinase to dissolve fibrin and aid in spread, and beta-lactamase for drug resistance.Medical Laboratory Manual For Tropical Countries vol two

Depending on the strain, S. aureus is capable of secreting several exotoxins, which can be categorized into three groups. Many of these toxins are associated with specific diseases.{{cite journal | vauthors = Dinges MM, Orwin PM, Schlievert PM | title = Exotoxins of Staphylococcus aureus | journal = Clinical Microbiology Reviews | volume = 13 | issue = 1 | pages = 16–34, table of contents | date = January 2000 | pmid = 10627489 | pmc = 88931 | doi = 10.1128/cmr.13.1.16 }}

;Superantigens

:Antigens known as superantigens can induce toxic shock syndrome (TSS). This group comprises 25 staphylococcal enterotoxins (SEs) which have been identified to date and named alphabetically (SEA–SEZ),{{cite journal | vauthors = Etter D, Schelin J, Schuppler M, Johler S | title = Staphylococcal Enterotoxin C-An Update on SEC Variants, Their Structure and Properties, and Their Role in Foodborne Intoxications | journal = Toxins | volume = 12 | issue = 9 | pages = 584 | date = September 2020 | pmid = 32927913 | pmc = 7551944 | doi = 10.3390/toxins12090584 | doi-access = free }} including enterotoxin type B as well as the toxic shock syndrome toxin TSST-1 which causes TSS associated with tampon use. Toxic shock syndrome is characterized by fever, erythematous rash, low blood pressure, shock, multiple organ failure, and skin peeling. Lack of antibody to TSST-1 plays a part in the pathogenesis of TSS. Other strains of S. aureus can produce an enterotoxin that is the causative agent of a type of gastroenteritis. This form of gastroenteritis is self-limiting, characterized by vomiting and diarrhea 1–6 hours after ingestion of the toxin, with recovery in 8 to 24 hours. Symptoms include nausea, vomiting, diarrhea, and major abdominal pain.{{cite journal | vauthors = Jarraud S, Peyrat MA, Lim A, Tristan A, Bes M, Mougel C, Etienne J, Vandenesch F, Bonneville M, Lina G | title = egc, a highly prevalent operon of enterotoxin gene, forms a putative nursery of superantigens in Staphylococcus aureus | journal = Journal of Immunology | volume = 166 | issue = 1 | pages = 669–677 | date = January 2001 | pmid = 11123352 | doi = 10.4049/jimmunol.166.1.669 | doi-access = free }}

{{anchor|Exfoliative toxins}}

;Exfoliative toxins

{{See also|Exfoliatin}}

: Exfoliative toxins are exotoxins implicated in the disease staphylococcal scalded skin syndrome (SSSS), which occurs most commonly in infants and young children. It also may occur as epidemics in hospital nurseries. The protease activity of the exfoliative toxins causes peeling of the skin observed with SSSS.{{cite journal | vauthors = Becker K, Friedrich AW, Lubritz G, Weilert M, Peters G, Von Eiff C | title = Prevalence of genes encoding pyrogenic toxin superantigens and exfoliative toxins among strains of Staphylococcus aureus isolated from blood and nasal specimens | journal = Journal of Clinical Microbiology | volume = 41 | issue = 4 | pages = 1434–9 | date = April 2003 | pmid = 12682126 | pmc = 153929 | doi = 10.1128/jcm.41.4.1434-1439.2003 }}

;Other toxins

: Staphylococcal toxins that act on cell membranes include alpha toxin, beta toxin, delta toxin, and several bicomponent toxins. Strains of S. aureus can host phages, such as the prophage Φ-PVL that produces Panton-Valentine leukocidin (PVL), to increase virulence. The bicomponent toxin PVL is associated with severe necrotizing pneumonia in children.{{cite journal | vauthors = Lina G, Piémont Y, Godail-Gamot F, Bes M, Peter MO, Gauduchon V, Vandenesch F, Etienne J | title = Involvement of Panton-Valentine leukocidin-producing Staphylococcus aureus in primary skin infections and pneumonia | journal = Clinical Infectious Diseases | volume = 29 | issue = 5 | pages = 1128–32 | date = November 1999 | pmid = 10524952 | doi = 10.1086/313461 | doi-access = free }}{{cite journal | vauthors = Gillet Y, Issartel B, Vanhems P, Fournet JC, Lina G, Bes M, Vandenesch F, Piémont Y, Brousse N, Floret D, Etienne J | title = Association between Staphylococcus aureus strains carrying gene for Panton-Valentine leukocidin and highly lethal necrotising pneumonia in young immunocompetent patients | journal = Lancet | volume = 359 | issue = 9308 | pages = 753–9 | date = March 2002 | pmid = 11888586 | doi = 10.1016/S0140-6736(02)07877-7 | s2cid = 20400336 }} As [http://reannecy.org/documents/Reanimation_Bibliographie/INFECTIOLOGIE/INFECTION%20PAR%20GERMES/BACTERIES/STAPH/2002%20PNP%20necrosante%20et%20panton%20valentine%20lancet.pdf PDF] {{webarchive|url=https://web.archive.org/web/20140714163825/http://reannecy.org/documents/Reanimation_Bibliographie/INFECTIOLOGIE/INFECTION%20PAR%20GERMES/BACTERIES/STAPH/2002%20PNP%20necrosante%20et%20panton%20valentine%20lancet.pdf |date=14 July 2014 }} The genes encoding the components of PVL are encoded on a bacteriophage found in community-associated MRSA strains.{{citation needed|date=February 2017}}

{{See also|Type VII secretion system|l1=Type VII secretion system (T7SS)}}

A secretion system is a highly specialised multi-protein unit that is embedded in the cell envelope with the function of translocating effector proteins from inside of the cell to the extracellular space or into a target host cytosol. The exact structure and function of T7SS is yet to be fully elucidated. Currently, four proteins are known components of S. aureus type VII secretion system; EssC is a large integral membrane ATPase – which most likely powers the secretion systems and has been hypothesised forming part of the translocation channel. The other proteins are EsaA, EssB, EssA, that are membrane proteins that function alongside EssC to mediate protein secretion. The exact mechanism of how substrates reach the cell surface is unknown, as is the interaction of the three membrane proteins with each other and EssC.{{cite journal | vauthors = Bowman L, Palmer T | title = The Type VII Secretion System of Staphylococcus | journal = Annual Review of Microbiology | volume = 75 | issue = 1 | pages = 471–494 | date = October 2021 | pmid = 34343022 | doi = 10.1146/annurev-micro-012721-123600 | s2cid = 236915377 }}

T7 dependent effector proteins

EsaD is DNA endonuclease toxin secreted by S. aureus, has been shown to inhibit growth of competitor S. aureus strain in vitro.{{cite journal | vauthors = Cao Z, Casabona MG, Kneuper H, Chalmers JD, Palmer T | title = The type VII secretion system of Staphylococcus aureus secretes a nuclease toxin that targets competitor bacteria | journal = Nature Microbiology | volume = 2 | issue = 1 | pages = 16183 | date = October 2016 | pmid = 27723728 | pmc = 5325307 | doi = 10.1038/nmicrobiol.2016.183 }} EsaD is cosecreted with chaperone EsaE, which stabilises EsaD structure and brings EsaD to EssC for secretion. Strains that produce EsaD also co-produce EsaG, a cytoplasmic anti-toxin that protects the producer strain from EsaD's toxicity.

TspA is another toxin that mediates intraspecies competition. It is a bacteriostatic toxin that has a membrane depolarising activity facilitated by its C-terminal domain. Tsai is a transmembrane protein that confers immunity to the producer strain of TspA, as well as the attacked strains. There is genetic variability of the C-terminal domain of TspA therefore, it seems like the strains may produce different TspA variants to increase competitiveness.{{cite journal | vauthors = Ulhuq FR, Gomes MC, Duggan GM, Guo M, Mendonca C, Buchanan G, Chalmers JD, Cao Z, Kneuper H, Murdoch S, Thomson S, Strahl H, Trost M, Mostowy S, Palmer T | title = A membrane-depolarizing toxin substrate of the Staphylococcus aureus type VII secretion system mediates intraspecies competition | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 117 | issue = 34 | pages = 20836–47 | date = August 2020 | pmid = 32769205 | pmc = 7456083 | doi = 10.1073/pnas.2006110117 | bibcode = 2020PNAS..11720836U | doi-access = free }}

Toxins that play a role in intraspecies competition confers an advantage by promoting successful colonisation in polymicrobial communities such as the nasopharynx and lung by outcompeting lesser strains.

There are also T7 effector proteins that play role a in pathogenesis, for example mutational studies of S. aureus have suggested that EsxB and EsxC contribute to persistent infection in a murine abscess model.{{cite journal | vauthors = Burts ML, Williams WA, DeBord K, Missiakas DM | title = EsxA and EsxB are secreted by an ESAT-6-like system that is required for the pathogenesis of Staphylococcus aureus infections | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 102 | issue = 4 | pages = 1169–74 | date = January 2005 | pmid = 15657139 | pmc = 545836 | doi = 10.1073/pnas.0405620102 | bibcode = 2005PNAS..102.1169B | doi-access = free }}

EsxX has been implicated in neutrophil lysis, therefore suggested as contributing to the evasion of host immune system. Deletion of essX in S. aureus resulted in significantly reduced resistance to neutrophils and reduced virulence in murine skin and blood infection models.{{cite journal | vauthors = Dai Y, Wang Y, Liu Q, Gao Q, Lu H, Meng H, Qin J, Hu M, Li M | title = A Novel ESAT-6 Secretion System-Secreted Protein EsxX of Community-Associated Staphylococcus aureus Lineage ST398 Contributes to Immune Evasion and Virulence | journal = Frontiers in Microbiology | volume = 8 | pages = 819 | date = 2017-05-05 | pmid = 28529509 | pmc = 5418362 | doi = 10.3389/fmicb.2017.00819 | doi-access = free }}

Altogether, T7SS and known secreted effector proteins are a strategy of pathogenesis by improving fitness against competitor S. aureus species as well as increased virulence via evading the innate immune system and optimising persistent infections.{{citation needed|date=August 2022}}

The list of small RNAs involved in the control of bacterial virulence in S. aureus is growing. This can be facilitated by factors such as increased biofilm formation in the presence of increased levels of such small RNAs.{{cite journal | vauthors = Kim S, Reyes D, Beaume M, Francois P, Cheung A | title = Contribution of teg49 small RNA in the 5' upstream transcriptional region of sarA to virulence in Staphylococcus aureus | journal = Infection and Immunity | volume = 82 | issue = 10 | pages = 4369–79 | date = October 2014 | pmid = 25092913 | pmc = 4187880 | doi = 10.1128/iai.02002-14 }} For example, RNAIII,{{cite journal | vauthors = Chevalier C, Boisset S, Romilly C, Masquida B, Fechter P, Geissmann T, Vandenesch F, Romby P | title = Staphylococcus aureus RNAIII binds to two distant regions of coa mRNA to arrest translation and promote mRNA degradation | journal = PLOS Pathogens | volume = 6 | issue = 3 | pages = e1000809 | date = March 2010 | pmid = 20300607 | pmc = 2837412 | doi = 10.1371/journal.ppat.1000809 | doi-access = free }} SprD,{{cite journal | vauthors = Chabelskaya S, Gaillot O, Felden B | title = A Staphylococcus aureus small RNA is required for bacterial virulence and regulates the expression of an immune-evasion molecule | journal = PLOS Pathogens | volume = 6 | issue = 6 | pages = e1000927 | date = June 2010 | pmid = 20532214 | pmc = 2880579 | doi = 10.1371/journal.ppat.1000927 | doi-access = free }} SprC,{{cite journal | vauthors = Le Pabic H, Germain-Amiot N, Bordeau V, Felden B | title = A bacterial regulatory RNA attenuates virulence, spread and human host cell phagocytosis | journal = Nucleic Acids Research | volume = 43 | issue = 19 | pages = 9232–48 | date = October 2015 | pmid = 26240382 | pmc = 4627067 | doi = 10.1093/nar/gkv783 }}{{cite journal | vauthors = Mauro T, Rouillon A, Felden B | title = Insights into the regulation of small RNA expression: SarA represses the expression of two sRNAs in Staphylococcus aureus | journal = Nucleic Acids Research | volume = 44 | issue = 21 | pages = 10186–200 | date = December 2016 | pmid = 27596601 | pmc = 5137438 | doi = 10.1093/nar/gkw777 }} RsaE,{{cite journal | vauthors = Bohn C, Rigoulay C, Chabelskaya S, Sharma CM, Marchais A, Skorski P, Borezée-Durant E, Barbet R, Jacquet E, Jacq A, Gautheret D, Felden B, Vogel J, Bouloc P | title = Experimental discovery of small RNAs in Staphylococcus aureus reveals a riboregulator of central metabolism | journal = Nucleic Acids Research | volume = 38 | issue = 19 | pages = 6620–36 | date = October 2010 | pmid = 20511587 | pmc = 2965222 | doi = 10.1093/nar/gkq462 }} SprA1,{{cite journal | vauthors = Sayed N, Jousselin A, Felden B | title = A cis-antisense RNA acts in trans in Staphylococcus aureus to control translation of a human cytolytic peptide | journal = Nature Structural & Molecular Biology | volume = 19 | issue = 1 | pages = 105–112 | date = December 2011 | pmid = 22198463 | doi = 10.1038/nsmb.2193 | s2cid = 8217681 | url = https://www.hal.inserm.fr/inserm-00696345/file/NSMBfinal.pdf }} SSR42,{{cite journal | vauthors = Morrison JM, Miller EW, Benson MA, Alonzo F, Yoong P, Torres VJ, Hinrichs SH, Dunman PM | title = Characterization of SSR42, a novel virulence factor regulatory RNA that contributes to the pathogenesis of a Staphylococcus aureus USA300 representative | journal = Journal of Bacteriology | volume = 194 | issue = 11 | pages = 2924–38 | date = June 2012 | pmid = 22493015 | pmc = 3370614 | doi = 10.1128/JB.06708-11 }} ArtR,{{cite journal | vauthors = Xue T, Zhang X, Sun H, Sun B | title = ArtR, a novel sRNA of Staphylococcus aureus, regulates α-toxin expression by targeting the 5' UTR of sarT mRNA | journal = Medical Microbiology and Immunology | volume = 203 | issue = 1 | pages = 1–12 | date = February 2014 | pmid = 23955428 | doi = 10.1007/s00430-013-0307-0 | s2cid = 18371872 }} SprX, Teg49, and IsrR.{{cite journal | vauthors = Coronel-Tellez RH, Pospiech M, Barrault M, Liu W, Bordeau V, Vasnier C, Felden B, Sargueil B, Bouloc P | title = sRNA-controlled iron sparing response in Staphylococci | journal = Nucleic Acids Research | volume = 50 | issue = 15 | pages = 8529–8546 | date = August 2022 | pmid = 35904807| pmc = 9410917 | doi = 10.1093/nar/gkac648 }}

Host neutrophils cause DNA double-strand breaks in S. aureus through the production of reactive oxygen species.{{cite journal |vauthors=Ha KP, Clarke RS, Kim GL, Brittan JL, Rowley JE, Mavridou DA, Parker D, Clarke TB, Nobbs AH, Edwards AM |title=Staphylococcal DNA Repair Is Required for Infection |journal=mBio |volume=11 |issue=6 |pages=e02288-20 |date=November 2020 |pmid=33203752 |pmc=7683395 |doi=10.1128/mBio.02288-20 }} For infection of a host to be successful, S. aureus must survive such damages caused by the hosts' defenses. The two protein complex RexAB encoded by S. aureus is employed in the recombinational repair of DNA double-strand breaks.

Many mRNAs in S. aureus carry three prime untranslated regions (3'UTR) longer than 100 nucleotides, which may potentially have a regulatory function.{{cite journal | vauthors = Ruiz de los Mozos I, Vergara-Irigaray M, Segura V, Villanueva M, Bitarte N, Saramago M, Domingues S, Arraiano CM, Fechter P, Romby P, Valle J, Solano C, Lasa I, Toledo-Arana A | title = Base pairing interaction between 5'- and 3'-UTRs controls icaR mRNA translation in Staphylococcus aureus | journal = PLOS Genetics | volume = 9 | issue = 12 | pages = e1004001 | date = 2013 | pmid = 24367275 | pmc = 3868564 | doi = 10.1371/journal.pgen.1004001 | doi-access = free }}

Further investigation of icaR mRNA (mRNA coding for the repressor of the main expolysaccharidic compound of the bacteria biofilm matrix) demonstrated that the 3'UTR binding to the 5' UTR can interfere with the translation initiation complex and generate a double stranded substrate for RNase III. The interaction is between the UCCCCUG motif in the 3'UTR and the Shine-Dalagarno region at the 5'UTR. Deletion of the motif resulted in IcaR repressor accumulation and inhibition of biofilm development. The biofilm formation is the main cause of Staphylococcus implant infections.{{cite journal | vauthors = Arciola CR, Campoccia D, Speziale P, Montanaro L, Costerton JW | title = Biofilm formation in Staphylococcus implant infections. A review of molecular mechanisms and implications for biofilm-resistant materials | journal = Biomaterials | volume = 33 | issue = 26 | pages = 5967–82 | date = September 2012 | pmid = 22695065 | doi = 10.1016/j.biomaterials.2012.05.031 }}

Biofilms are groups of microorganisms, such as bacteria, that attach to each other and grow on wet surfaces.Vidyasagar, A. (2016). What Are Biofilms? Live Science. The S. aureus biofilm is embedded in a glycocalyx slime layer and can consist of teichoic acids, host proteins, extracellular DNA (eDNA) and sometimes polysaccharide intercellular antigen (PIA). S. aureus biofilms are important in disease pathogenesis, as they can contribute to antibiotic resistance and immune system evasion. S. aureus biofilm has high resistance to antibiotic treatments and host immune response. One hypothesis for explaining this is that the biofilm matrix protects the embedded cells by acting as a barrier to prevent antibiotic penetration. However, the biofilm matrix is composed with many water channels, so this hypothesis is becoming increasingly less likely, but a biofilm matrix possibly contains antibiotic‐degrading enzymes such as β-lactamases, which can prevent antibiotic penetration.{{cite journal | vauthors = de la Fuente-Núñez C, Reffuveille F, Fernández L, Hancock RE | title = Bacterial biofilm development as a multicellular adaptation: antibiotic resistance and new therapeutic strategies | journal = Current Opinion in Microbiology | volume = 16 | issue = 5 | pages = 580–9 | date = October 2013 | pmid = 23880136 | doi = 10.1016/j.mib.2013.06.013 }} Another hypothesis is that the conditions in the biofilm matrix favor the formation of persister cells, which are highly antibiotic-resistant, dormant bacterial cells. S. aureus biofilms also have high resistance to host immune response. Though the exact mechanism of resistance is unknown, S. aureus biofilms have increased growth under the presence of cytokines produced by the host immune response.{{cite journal | vauthors = McLaughlin RA, Hoogewerf AJ | title = Interleukin-1beta-induced growth enhancement of Staphylococcus aureus occurs in biofilm but not planktonic cultures | journal = Microbial Pathogenesis | volume = 41 | issue = 2–3 | pages = 67–79 | date = August 2006 | pmid = 16769197 | doi = 10.1016/j.micpath.2006.04.005 }} Host antibodies are less effective for S. aureus biofilm due to the heterogeneous antigen distribution, where an antigen may be present in some areas of the biofilm, but completely absent from other areas.

Studies in biofilm development have shown to be related to changes in gene expression. There are specific genes that were found to be crucial in the different biofilm growth stages. Two of these genes include rocD and gudB, which encode for the enzyme's ornithine-oxo-acid transaminase and glutamate dehydrogenase, which are important for amino acid metabolism. Studies have shown biofilm development rely on amino acids glutamine and glutamate for proper metabolic functions.{{cite journal | vauthors = Nassar R, Hachim M, Nassar M, Kaklamanos EG, Jamal M, Williams D, Senok A | title = Microbial Metabolic Genes Crucial for S. aureus Biofilms: An Insight From Re-analysis of Publicly Available Microarray Datasets | language = English | journal = Frontiers in Microbiology | volume = 11 | pages = 607002 | date = 2021 | pmid = 33584569 | pmc = 7876462 | doi = 10.3389/fmicb.2020.607002 | doi-access = free }}

;Protein A

Protein A is anchored to staphylococcal peptidoglycan pentaglycine bridges (chains of five glycine residues) by the transpeptidase sortase A.{{cite journal | vauthors = Schneewind O, Fowler A, Faull KF | title = Structure of the cell wall anchor of surface proteins in Staphylococcus aureus | journal = Science | volume = 268 | issue = 5207 | pages = 103–6 | date = April 1995 | pmid = 7701329 | doi = 10.1126/science.7701329 | bibcode = 1995Sci...268..103S }} Protein A, an IgG-binding protein, binds to the Fc region of an antibody. In fact, studies involving mutation of genes coding for protein A resulted in a lowered virulence of S. aureus as measured by survival in blood, which has led to speculation that protein A-contributed virulence requires binding of antibody Fc regions.{{cite journal | vauthors = Patel AH, Nowlan P, Weavers ED, Foster T | title = Virulence of protein A-deficient and alpha-toxin-deficient mutants of Staphylococcus aureus isolated by allele replacement | journal = Infection and Immunity | volume = 55 | issue = 12 | pages = 3103–10 | date = December 1987 | pmid = 3679545 | pmc = 260034 | doi = 10.1128/IAI.55.12.3103-3110.1987 }}

Protein A in various recombinant forms has been used for decades to bind and purify a wide range of antibodies by immunoaffinity chromatography. Transpeptidases, such as the sortases responsible for anchoring factors like protein A to the staphylococcal peptidoglycan, are being studied in hopes of developing new antibiotics to target MRSA infections.{{cite journal | vauthors = Zhu J, Lu C, Standland M, Lai E, Moreno GN, Umeda A, Jia X, Zhang Z | title = Single mutation on the surface of Staphylococcus aureus Sortase A can disrupt its dimerization | journal = Biochemistry | volume = 47 | issue = 6 | pages = 1667–74 | date = February 2008 | pmid = 18193895 | doi = 10.1021/bi7014597 }}

File:Staphylococcus aureus on TSA.jpg: The strain is producing a yellow pigment staphyloxanthin. ]]

;Staphylococcal pigments

Some strains of S. aureus are capable of producing staphyloxanthin – a golden-coloured carotenoid pigment. This pigment acts as a virulence factor, primarily by being a bacterial antioxidant which helps the microbe evade the reactive oxygen species which the host immune system uses to kill pathogens.{{cite journal | vauthors = Clauditz A, Resch A, Wieland KP, Peschel A, Götz F | title = Staphyloxanthin plays a role in the fitness of Staphylococcus aureus and its ability to cope with oxidative stress | journal = Infection and Immunity | volume = 74 | issue = 8 | pages = 4950–3 | date = August 2006 | pmid = 16861688 | pmc = 1539600 | doi = 10.1128/IAI.00204-06 }}{{cite journal | vauthors = Liu GY, Essex A, Buchanan JT, Datta V, Hoffman HM, Bastian JF, Fierer J, Nizet V | title = Staphylococcus aureus golden pigment impairs neutrophil killing and promotes virulence through its antioxidant activity | journal = The Journal of Experimental Medicine | volume = 202 | issue = 2 | pages = 209–215 | date = July 2005 | pmid = 16009720 | pmc = 2213009 | doi = 10.1084/jem.20050846 }}

Mutant strains of S. aureus modified to lack staphyloxanthin are less likely to survive incubation with an oxidizing chemical, such as hydrogen peroxide, than pigmented strains. Mutant colonies are quickly killed when exposed to human neutrophils, while many of the pigmented colonies survive. In mice, the pigmented strains cause lingering abscesses when inoculated into wounds, whereas wounds infected with the unpigmented strains quickly heal.{{citation needed|date=December 2022}}

These tests suggest the Staphylococcus strains use staphyloxanthin as a defence against the normal human immune system. Drugs designed to inhibit the production of staphyloxanthin may weaken the bacterium and renew its susceptibility to antibiotics. In fact, because of similarities in the pathways for biosynthesis of staphyloxanthin and human cholesterol, a drug developed in the context of cholesterol-lowering therapy was shown to block S. aureus pigmentation and disease progression in a mouse infection model.{{cite journal | vauthors = Liu CI, Liu GY, Song Y, Yin F, Hensler ME, Jeng WY, Nizet V, Wang AH, Oldfield E | title = A cholesterol biosynthesis inhibitor blocks Staphylococcus aureus virulence | journal = Science | volume = 319 | issue = 5868 | pages = 1391–4 | date = March 2008 | pmid = 18276850 | pmc = 2747771 | doi = 10.1126/science.1153018 | bibcode = 2008Sci...319.1391L }}

;Resistance to Hypothiocyanous Acid (HOSCN)

Staphylococcus aureus has developed an adaptive mechanism to tolerate hypothiocyanous acid (HOSCN), a potent oxidant produced by the human immune system.{{cite journal |last1=Barrett |first1=T. J. |last2=Hawkins |first2=C. L. |year=2012 |title=Hypothiocyanous Acid: Benign or Deadly? |journal=Chemical Research in Toxicology |volume=25 |issue=2 |pages=263–273 |doi=10.1021/tx200219s|pmid=22053976 }}{{cite journal |last1=Loi |first1=V. Van |last2=Busche |first2=T. |last3=Schnaufer |first3=F. |last4=Kalinowski |first4=J. |last5=Antelmann |first5=H. |year=2023 |title=The neutrophil oxidant hypothiocyanous acid causes a thiol-specific stress response and an oxidative shift of the bacillithiol redox potential in Staphylococcus aureus |journal=Microbiology Spectrum |volume=11 |issue=6 |pages=e03252-23 |doi=10.1128/spectrum.03252-23|pmid=37930020 |pmc=10715087 }} Compared to other methicillin-resistant S. aureus (MRSA) strains and bacterial pathogens such as Pseudomonas aeruginosa, Escherichia coli, and Streptococcus pneumoniae, S. aureus exhibits greater resistance to HOSCN.{{cite journal |last1=Shearer |first1=H. L. |last2=Loi |first2=V. V. |last3=Weiland |first3=P. |last4=Bange |first4=G. |last5=Altegoer |first5=F. |last6=Hampton |first6=M. B. |last7=Antelmann |first7=H. |last8=Dickerhof |first8=N. |year=2023 |title=MerA functions as a hypothiocyanous acid reductase and defense mechanism in Staphylococcus aureus |journal=Molecular Microbiology |volume=119 |issue=4 |pages=456–470 |doi=10.1111/MMI.15035|doi-access=free |pmid=36779383 }}

This resistance is linked to the merA gene, which encodes a flavoprotein disulfide reductase (FDR) enzyme. S. aureus MerA shares similarities with HOSCN reductases from other bacteria, including S. pneumoniae (50% sequence identity, 66% positives) and RclA in E. coli (50% sequence identity, 65% positives). These enzymes play a crucial role in oxidative stress defense by using NADPH as a cofactor to reduce disulfide bonds, thereby mitigating the oxidative damage caused by HOSCN.{{cite journal |last1=Shearer |first1=H. L. |last2=Pace |first2=P. E. |last3=Paton |first3=J. C. |last4=Hampton |first4=M. B. |last5=Dickerhof |first5=N. |year=2022 |title=A newly identified flavoprotein disulfide reductase Har protects Streptococcus pneumoniae against hypothiocyanous acid |journal=Journal of Biological Chemistry |volume=298 |issue=9 |pages=102359 |doi=10.1016/J.JBC.2022.102359|doi-access=free |pmid=35952759 |pmc=9483559 }} This mechanism enhances S. aureus survival within the host by counteracting the immune system’s oxidative attack.

Functional characterization of MerA has revealed that the amino acid residue Cys43 (C43) is essential for its enzymatic activity against HOSCN. Additionally, the expression of merA in S. aureus is regulated by the hypR gene, a transcriptional suppressor that modulates the bacterial response to oxidative stress.

File:Staph sputum.JPG

Depending upon the type of infection present, an appropriate specimen is obtained accordingly and sent to the laboratory for definitive identification by using biochemical or enzyme-based tests. A Gram stain is first performed to guide the way, which should show typical Gram-positive bacteria, cocci, in clusters. Second, the isolate is cultured on mannitol salt agar, which is a selective medium with 7.5% NaCl that allows S. aureus to grow, producing yellow-colored colonies as a result of mannitol fermentation and subsequent drop in the medium's pH.{{cite journal| vauthors = Shields P, Tsang AY |date=2006-10-09|title=Mannitol Salt Agar Plates Protocols|url=https://www.asmscience.org/content/education/protocol/protocol.3034|access-date=2020-12-31|website=www.asmscience.org|language=en}}{{cite web|date=2020-01-14|title=Mannitol Salt Agar (MSA) {{!}} Culture Media|url=https://microbenotes.com/mannitol-salt-agar-msa/|access-date=2020-12-31|website=Microbe Notes|language=en-US}}

Furthermore, for differentiation on the species level, catalase (positive for all Staphylococcus species), coagulase (fibrin clot formation, positive for S. aureus), DNAse (zone of clearance on DNase agar), lipase (a yellow color and rancid odor smell), and phosphatase (a pink color) tests are all done. For staphylococcal food poisoning, phage typing can be performed to determine whether the staphylococci recovered from the food were the source of infection.{{cite journal | vauthors = Saint-Martin M, Charest G, Desranleau JM | title = Bacteriophage typing in investigations of staphylococcal food-poisoning outbreaks | journal = Canadian Journal of Public Health | volume = 42 | issue = 9 | pages = 351–8 | date = September 1951 | pmid = 14879282 | url = https://www.jstor.org/stable/41980177 | jstor = 41980177 }}

Diagnostic microbiology laboratories and reference laboratories are key for identifying outbreaks and new strains of S. aureus. Recent genetic advances have enabled reliable and rapid techniques for the identification and characterization of clinical isolates of S. aureus in real time. These tools support infection control strategies to limit bacterial spread and ensure the appropriate use of antibiotics. Quantitative PCR is increasingly being used to identify outbreaks of infection.{{cite book |chapter-url=http://www.horizonpress.com/staph|vauthors=Francois P, Schrenzel J|year=2008|chapter=Rapid Diagnosis and Typing of Staphylococcus aureus|title=Staphylococcus: Molecular Genetics|publisher=Caister Academic Press |isbn=978-1-904455-29-5}}{{cite book | editor = Mackay IM | title = Real-Time PCR in Microbiology: From Diagnosis to Characterization | publisher = Caister Academic Press | year = 2007 | isbn = 978-1-904455-18-9}}

When observing the evolvement of S. aureus and its ability to adapt to each modified antibiotic, two basic methods known as "band-based" or "sequence-based" are employed.{{cite journal | vauthors = Deurenberg RH, Stobberingh EE | title = The evolution of Staphylococcus aureus | journal = Infection, Genetics and Evolution | volume = 8 | issue = 6 | pages = 747–763 | date = December 2008 | pmid = 18718557 | doi = 10.1016/j.meegid.2008.07.007 | bibcode = 2008InfGE...8..747D }} Keeping these two methods in mind, other methods such as multilocus sequence typing (MLST), pulsed-field gel electrophoresis (PFGE), bacteriophage typing, spa locus typing, and SCCmec typing are often conducted more than others.{{cite journal | vauthors = Aires de Sousa M, Conceição T, Simas C, de Lencastre H | title = Comparison of genetic backgrounds of methicillin-resistant and -susceptible Staphylococcus aureus isolates from Portuguese hospitals and the community | journal = Journal of Clinical Microbiology | volume = 43 | issue = 10 | pages = 5150–7 | date = October 2005 | pmid = 16207977 | pmc = 1248511 | doi = 10.1128/JCM.43.10.5150-5157.2005 }} With these methods, it can be determined where strains of MRSA originated and also where they are currently.{{cite journal | vauthors = Kim J | year = 2009 | title = Understanding the Evolution of Methicillin-Resistant Staphylococcus aureus | journal = Clinical Microbiology Newsletter | volume = 31 | issue = 3| pages = 17–23 | doi = 10.1016/j.clinmicnews.2009.01.002 }}

With MLST, this technique of typing uses fragments of several housekeeping genes known as aroE, glpF, gmk, pta, tip, and yqiL. These sequences are then assigned a number which give to a string of several numbers that serve as the allelic profile. Although this is a common method, a limitation about this method is the maintenance of the microarray which detects newly allelic profiles, making it a costly and time-consuming experiment.

With PFGE, a method which is still very much used dating back to its first success in 1980s, remains capable of helping differentiate MRSA isolates. To accomplish this, the technique uses multiple gel electrophoresis, along with a voltage gradient to display clear resolutions of molecules. The S. aureus fragments then transition down the gel, producing specific band patterns that are later compared with other isolates in hopes of identifying related strains. Limitations of the method include practical difficulties with uniform band patterns and PFGE sensitivity as a whole.{{citation needed|date=August 2022}}

Spa locus typing is also considered a popular technique that uses a single locus zone in a polymorphic region of S. aureus to distinguish any form of mutations. Although this technique is often inexpensive and less time-consuming, the chance of losing discriminatory power making it hard to differentiate between MLST clonal complexes exemplifies a crucial limitation.{{citation needed|date=August 2022}}

For susceptible strains, the treatment of choice for S. aureus infection is penicillin. An antibiotic derived from some Penicillium fungal species, penicillin inhibits the formation of peptidoglycan cross-linkages that provide the rigidity and strength in a bacterial cell wall. The four-membered β-lactam ring of penicillin is bound to enzyme DD-transpeptidase, an enzyme that when functional, cross-links chains of peptidoglycan that form bacterial cell walls. The binding of β-lactam to DD-transpeptidase inhibits the enzyme's functionality and it can no longer catalyze the formation of the cross-links. As a result, cell wall formation and degradation are imbalanced, thus resulting in cell death. In most countries, however, penicillin resistance is extremely common (>90%), and first-line therapy is most commonly a penicillinase-resistant β-lactam antibiotic (for example, oxacillin or flucloxacillin, both of which have the same mechanism of action as penicillin) or vancomycin, depending on local resistance patterns. Combination therapy with gentamicin may be used to treat serious infections, such as endocarditis,{{cite journal | vauthors = Korzeniowski O, Sande MA | title = Combination antimicrobial therapy for Staphylococcus aureus endocarditis in patients addicted to parenteral drugs and in nonaddicts: A prospective study | journal = Annals of Internal Medicine | volume = 97 | issue = 4 | pages = 496–503 | date = October 1982 | pmid = 6751182 | doi = 10.7326/0003-4819-97-4-496 }}{{cite journal | vauthors = Bayer AS, Bolger AF, Taubert KA, Wilson W, Steckelberg J, Karchmer AW, Levison M, Chambers HF, Dajani AS, Gewitz MH, Newburger JW, Gerber MA, Shulman ST, Pallasch TJ, Gage TW, Ferrieri P | title = Diagnosis and management of infective endocarditis and its complications | journal = Circulation | volume = 98 | issue = 25 | pages = 2936–48 | year = 1998 | pmid = 9860802 | doi = 10.1161/01.CIR.98.25.2936 | doi-access = free }} but its use is controversial because of the high risk of damage to the kidneys.{{cite journal | vauthors = Cosgrove SE, Vigliani GA, Fowler VG, Abrutyn E, Corey GR, Levine DP, Rupp ME, Chambers HF, Karchmer AW, Boucher HW | title = Initial low-dose gentamicin for Staphylococcus aureus bacteremia and endocarditis is nephrotoxic | journal = Clinical Infectious Diseases | volume = 48 | issue = 6 | pages = 713–721 | date = March 2009 | pmid = 19207079 | doi = 10.1086/597031 | doi-access = free }} The duration of treatment depends on the site of infection and on severity. Adjunctive rifampicin has been historically used in the management of S aureus bacteraemia, but randomised controlled trial evidence has shown this to be of no overall benefit over standard antibiotic therapy.{{cite journal | vauthors = Thwaites GE, Scarborough M, Szubert A, Nsutebu E, Tilley R, Greig J, Wyllie SA, Wilson P, Auckland C, Cairns J, Ward D, Lal P, Guleri A, Jenkins N, Sutton J, Wiselka M, Armando GR, Graham C, Chadwick PR, Barlow G, Gordon NC, Young B, Meisner S, McWhinney P, Price DA, Harvey D, Nayar D, Jeyaratnam D, Planche T, Minton J, Hudson F, Hopkins S, Williams J, Török ME, Llewelyn MJ, Edgeworth JD, Walker AS | title = Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial | journal = Lancet | volume = 391 | issue = 10121 | pages = 668–678 | date = February 2018 | pmid = 29249276 | pmc = 5820409 | doi = 10.1016/S0140-6736(17)32456-X }}

Antibiotic resistance in S. aureus was uncommon when penicillin was first introduced in 1943. Indeed, the original Petri dish on which Alexander Fleming of Imperial College London observed the antibacterial activity of the Penicillium fungus was growing a culture of S. aureus. By 1950, 40% of hospital S. aureus isolates were penicillin-resistant; by 1960, this had risen to 80%.{{cite journal | vauthors = Chambers HF | title = The changing epidemiology of Staphylococcus aureus? | journal = Emerging Infectious Diseases | volume = 7 | issue = 2 | pages = 178–182 | year = 2001 | pmid = 11294701 | pmc = 2631711 | doi = 10.3201/eid0702.010204 }}

Methicillin-resistant Staphylococcus aureus (MRSA, often pronounced {{IPAc-en|ˈ|m|ɜr|s|ə}} or {{IPAc-en|ɛ|m|_|ɑːr|_|ɛ|s|_|eɪ}}), is one of a number of greatly feared strains of S. aureus which have become resistant to most β-lactam antibiotics. For this reason, vancomycin, a glycopeptide antibiotic, is commonly used to combat MRSA. Vancomycin inhibits the synthesis of peptidoglycan, but unlike β-lactam antibiotics, glycopeptide antibiotics target and bind to amino acids in the cell wall, preventing peptidoglycan cross-linkages from forming. MRSA strains are most often found associated with institutions such as hospitals, but are becoming increasingly prevalent in community-acquired infections.{{citation needed|date=August 2022}}

Minor skin infections can be treated with triple antibiotic ointment.{{cite journal | vauthors = Bonomo RA, Van Zile PS, Li Q, Shermock KM, McCormick WG, Kohut B | title = Topical triple-antibiotic ointment as a novel therapeutic choice in wound management and infection prevention: a practical perspective | journal = Expert Review of Anti-Infective Therapy | volume = 5 | issue = 5 | pages = 773–782 | date = October 2007 | pmid = 17914912 | doi = 10.1586/14787210.5.5.773 | s2cid = 31594289 }} One topical agent that is prescribed is mupirocin, a protein synthesis inhibitor that is produced naturally by Pseudomonas fluorescens and has seen success for treatment of S. aureus nasal carriage.

{{Main|Antimicrobial resistance}}

Image:Staphylococcus aureus, 50,000x, USDA, ARS, EMU.jpg: Its large capsule protects the organism from attack by the cow's immunological defenses.]]

Staphylococcus aureus was found to be the second leading pathogen for deaths associated with antimicrobial resistance in 2019.{{cite journal | vauthors = Murray CJ, Ikuta KS, Sharara F, Swetschinski L, Aguilar GR, Gray A, etal | collaboration = Antimicrobial Resistance Collaborators | title = Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis | language = English | journal = Lancet | volume = 399 | issue = 10325 | pages = 629–655 | date = February 2022 | pmid = 35065702 | pmc = 8841637 | doi = 10.1016/S0140-6736(21)02724-0 }}

Staphylococcal resistance to penicillin is mediated by penicillinase (a form of beta-lactamase) production: an enzyme that cleaves the β-lactam ring of the penicillin molecule, rendering the antibiotic ineffective. Penicillinase-resistant β-lactam antibiotics, such as methicillin, nafcillin, oxacillin, cloxacillin, dicloxacillin, and flucloxacillin are able to resist degradation by staphylococcal penicillinase.{{citation needed|date=December 2022}}

File:Staphylococcus aureus susceptibility.jpg

Resistance to methicillin is mediated via the mec operon, part of the staphylococcal cassette chromosome mec (SCCmec). SCCmec is a family of mobile genetic elements, which is a major driving force of S. aureus evolution. Resistance is conferred by the mecA gene, which codes for an altered penicillin-binding protein (PBP2a or PBP2') that has a lower affinity for binding β-lactams (penicillins, cephalosporins, and carbapenems). This allows for resistance to all β-lactam antibiotics, and obviates their clinical use during MRSA infections. Studies have explained that this mobile genetic element has been acquired by different lineages in separate gene transfer events, indicating that there is not a common ancestor of differing MRSA strains.{{cite journal | vauthors = Jamrozy D, Coll F, Mather AE, Harris SR, Harrison EM, MacGowan A, Karas A, Elston T, Estée Török M, Parkhill J, Peacock SJ | title = Evolution of mobile genetic element composition in an epidemic methicillin-resistant Staphylococcus aureus: temporal changes correlated with frequent loss and gain events | journal = BMC Genomics | volume = 18 | issue = 1 | pages = 684 | date = September 2017 | pmid = 28870171 | pmc = 5584012 | doi = 10.1186/s12864-017-4065-z | doi-access = free }} One study suggests that MRSA sacrifices virulence, for example, toxin production and invasiveness, for survival and creation of biofilms{{cite journal | vauthors = Pozzi C, Waters EM, Rudkin JK, Schaeffer CR, Lohan AJ, Tong P, Loftus BJ, Pier GB, Fey PD, Massey RC, O'Gara JP | title = Methicillin resistance alters the biofilm phenotype and attenuates virulence in Staphylococcus aureus device-associated infections | journal = PLOS Pathogens | volume = 8 | issue = 4 | pages = e1002626 | date = 2012-04-05 | pmid = 22496652 | pmc = 3320603 | doi = 10.1371/journal.ppat.1002626 | veditors = Sullam PM | doi-access = free }}

Aminoglycoside antibiotics, such as kanamycin, gentamicin, streptomycin, were once effective against staphylococcal infections until strains evolved mechanisms to inhibit the aminoglycosides' action, which occurs via protonated amine and/or hydroxyl interactions with the ribosomal RNA of the bacterial 30S ribosomal subunit.{{cite journal | vauthors = Carter AP, Clemons WM, Brodersen DE, Morgan-Warren RJ, Wimberly BT, Ramakrishnan V | title = Functional insights from the structure of the 30S ribosomal subunit and its interactions with antibiotics | journal = Nature | volume = 407 | issue = 6802 | pages = 340–8 | date = September 2000 | pmid = 11014183 | doi = 10.1038/35030019 | s2cid = 4408938 | bibcode = 2000Natur.407..340C | url = https://resolver.caltech.edu/CaltechAUTHORS:20181030-134119194 }} Three main mechanisms of aminoglycoside resistance mechanisms are currently and widely accepted: aminoglycoside modifying enzymes, ribosomal mutations, and active efflux of the drug out of the bacteria.{{citation needed|date=August 2022}}

Aminoglycoside-modifying enzymes inactivate the aminoglycoside by covalently attaching either a phosphate, nucleotide, or acetyl moiety to either the amine or the alcohol key functional group (or both groups) of the antibiotic. This changes the charge or sterically hinders the antibiotic, decreasing its ribosomal binding affinity. In S. aureus, the best-characterized aminoglycoside-modifying enzyme is aminoglycoside adenylyltransferase 4' IA (ANT(4')IA). This enzyme has been solved by X-ray crystallography.{{cite journal | vauthors = Sakon J, Liao HH, Kanikula AM, Benning MM, Rayment I, Holden HM | title = Molecular structure of kanamycin nucleotidyltransferase determined to 3.0-A resolution | journal = Biochemistry | volume = 32 | issue = 45 | pages = 11977–84 | date = November 1993 | pmid = 8218273 | doi = 10.1021/bi00096a006 }} The enzyme is able to attach an adenyl moiety to the 4' hydroxyl group of many aminoglycosides, including kanamycin and gentamicin.{{citation needed|date=August 2022}}

Glycopeptide resistance is typically mediated by acquisition of the vanA gene, which originates from the Tn1546 transposon found in a plasmid in enterococci and codes for an enzyme that produces an alternative peptidoglycan to which vancomycin will not bind.{{cite journal | vauthors = Arthur M, Courvalin P | title = Genetics and mechanisms of glycopeptide resistance in enterococci | journal = Antimicrobial Agents and Chemotherapy | volume = 37 | issue = 8 | pages = 1563–71 | date = August 1993 | pmid = 8215264 | pmc = 188020 | doi = 10.1128/AAC.37.8.1563 | publisher = ASM }}

Today, S. aureus has become resistant to many commonly used antibiotics. In the UK, only 2% of all S. aureus isolates are sensitive to penicillin, with a similar picture in the rest of the world. The β-lactamase-resistant penicillins (methicillin, oxacillin, cloxacillin, and flucloxacillin) were developed to treat penicillin-resistant S. aureus, and are still used as first-line treatment. Methicillin was the first antibiotic in this class to be used (it was introduced in 1959), but only two years later, the first case of methicillin-resistant Staphylococcus aureus (MRSA) was reported in England.{{cite journal | vauthors = Rolinson GN, Stevens S, Batchelor FR, Wood JC, Chain EB | title = Bacteriological studies on a new penicillin-BRL. 1241 | journal = Lancet | volume = 2 | issue = 7150 | pages = 564–7 | date = September 1960 | pmc = 1952878 | doi = 10.1136/bmj.1.5219.124-a | pmid = 14438510 }}

Despite this, MRSA generally remained an uncommon finding, even in hospital settings, until the 1990s, when the MRSA prevalence in hospitals exploded, and it is now endemic.{{cite journal | vauthors = Johnson AP, Aucken HM, Cavendish S, Ganner M, Wale MC, Warner M, Livermore DM, Cookson BD | title = Dominance of EMRSA-15 and -16 among MRSA causing nosocomial bacteraemia in the UK: analysis of isolates from the European Antimicrobial Resistance Surveillance System (EARSS) | journal = The Journal of Antimicrobial Chemotherapy | volume = 48 | issue = 1 | pages = 143–4 | date = July 2001 | pmid = 11418528 | doi = 10.1093/jac/48.1.143 | doi-access = free }} Now, methicillin-resistant Staphylococcus aureus (MRSA) is not only a human pathogen causing a variety of infections, such as skin and soft tissue infection (SSTI), pneumonia, and sepsis, but it also can cause disease in animals, known as livestock-associated MRSA (LA-MRSA).{{cite journal | vauthors = Chen CJ, Huang YC | title = Emergence of livestock-associated methicillin-resistant Staphylococcus aureus: Should it be a concern? | journal = Journal of the Formosan Medical Association = Taiwan Yi Zhi | volume = 117 | issue = 8 | pages = 658–661 | date = August 2018 | pmid = 29754805 | doi = 10.1016/j.jfma.2018.04.004 | s2cid = 21659477 | doi-access = free }}

MRSA infections in both the hospital and community setting are commonly treated with non-β-lactam antibiotics, such as clindamycin (a lincosamine) and co-trimoxazole (also commonly known as trimethoprim/sulfamethoxazole). Resistance to these antibiotics has also led to the use of new, broad-spectrum anti-Gram-positive antibiotics, such as linezolid, because of its availability as an oral drug. First-line treatment for serious invasive infections due to MRSA is currently glycopeptide antibiotics (vancomycin and teicoplanin). A number of problems with these antibiotics occur, such as the need for intravenous administration (no oral preparation is available), toxicity, and the need to monitor drug levels regularly by blood tests. Also, glycopeptide antibiotics do not penetrate very well into infected tissues (this is a particular concern with infections of the brain and meninges and in endocarditis). Glycopeptides must not be used to treat methicillin-sensitive S. aureus (MSSA), as outcomes are inferior.{{verify source|date=October 2011}}{{cite journal | vauthors = Blot SI, Vandewoude KH, Hoste EA, Colardyn FA | title = Outcome and attributable mortality in critically Ill patients with bacteremia involving methicillin-susceptible and methicillin-resistant Staphylococcus aureus | journal = Archives of Internal Medicine | volume = 162 | issue = 19 | pages = 2229–35 | date = October 2002 | pmid = 12390067 | doi = 10.1001/archinte.162.19.2229 | doi-access = free }}

Daptomycin is a cyclic lipopeptide antibiotic primarily used for treating Gram-positive bacterial infections, including those caused by Staphylococcus aureus. It was first approved in 2003 and is especially effective against resistant strains like methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Staphylococcus aureus (VRSA).

Daptomycin works in a unique way compared to other antibiotics. It including calcium-dependent membrane binding, disruption of membrane potentia and bacterial cell death.Daptomycin is FDA-approved for treating complicated skin and soft tissue infections  and bloodstream infections and right-sided infective endocarditis caused by S. aureus.{{Cite journal |last1=Pader |first1=Vera |last2=Hakim |first2=Sanika |last3=Painter |first3=Kimberley L. |last4=Wigneshweraraj |first4=Sivaramesh |last5=Clarke |first5=Thomas B. |last6=Edwards |first6=Andrew M. |date=2016-10-24 |title=Staphylococcus aureus inactivates daptomycin by releasing membrane phospholipids |url=https://www.nature.com/articles/nmicrobiol2016194 |journal=Nature Microbiology |language=en |volume=2 |issue=1 |page=16194 |doi=10.1038/nmicrobiol.2016.194 |pmid=27775684 |issn=2058-5276|hdl=10044/1/40119 |hdl-access=free }}

Serum triggers a high degree of tolerance to the lipopeptide antibiotic daptomycin and several other classes of antibiotic.Serum-induced daptomycin tolerance is due to two independent mechanisms. The first one is the activation of the GraRS two-component system.{{Cite journal |last1=Yang |first1=Soo-Jin |last2=Bayer |first2=Arnold S. |last3=Mishra |first3=Nagendra N. |last4=Meehl |first4=Michael |last5=Ledala |first5=Nagender |last6=Yeaman |first6=Michael R. |last7=Xiong |first7=Yan Q. |last8=Cheung |first8=Ambrose L. |date=2012-12-22 |title=The Staphylococcus aureus Two-Component Regulatory System, GraRS, Senses and Confers Resistance to Selected Cationic Antimicrobial Peptides |journal=Infection and Immunity |volume=80 |issue=1 |pages=74–81 |doi=10.1128/iai.05669-11 |pmc=3255649 |pmid=21986630}} The activation is triggered by the host defense LL-37. So that, bacteria can make more peptidoglycan to make the cell wall become thicker. This can make the tolerance of bacteria. The second one is the increase of cardiolipin abundance in the membrane.The serum-adapted bacteria can change their membrane composition. This change can reduce the binding of daptomycin to the bacteria’s membrane.{{Cite journal |last1=Ledger |first1=Elizabeth V. K. |last2=Mesnage |first2=Stéphane |last3=Edwards |first3=Andrew M. |date=2022-04-19 |title=Human serum triggers antibiotic tolerance in Staphylococcus aureus |journal=Nature Communications |language=en |volume=13 |issue=1 |pages=2041 |doi=10.1038/s41467-022-29717-3 |issn=2041-1723 |pmc=9018823 |pmid=35440121|bibcode=2022NatCo..13.2041L }}

Because of the high level of resistance to penicillins and because of the potential for MRSA to develop resistance to vancomycin, the U.S. Centers for Disease Control and Prevention has published guidelines{{Cite web |date=22 September 1995 |title=Recommendations for Preventing the Spread of Vancomycin Resistance Recommendations of the Hospital Infection Control Practices Advisory Committee (HICPAC) |url=http://wonder.cdc.gov/wonder/prevguid/m0039349/m0039349.asp |url-status=dead |archive-url=https://web.archive.org/web/20060923012326/http://wonder.cdc.gov/wonder/prevguid/m0039349/m0039349.asp |archive-date=23 September 2006 |website=CDC}} for the appropriate use of vancomycin. In situations where the incidence of MRSA infections is known to be high, the attending physician may choose to use a glycopeptide antibiotic until the identity of the infecting organism is known. After the infection is confirmed to be due to a methicillin-susceptible strain of S. aureus, treatment can be changed to flucloxacillin or even penicillin, as appropriate.{{citation needed|date=December 2022}}

Vancomycin-resistant S. aureus (VRSA) is a strain of S. aureus that has become resistant to the glycopeptides. The first case of vancomycin-intermediate S. aureus (VISA) was reported in Japan in 1996;{{cite journal | vauthors = Hiramatsu K, Hanaki H, Ino T, Yabuta K, Oguri T, Tenover FC | title = Methicillin-resistant Staphylococcus aureus clinical strain with reduced vancomycin susceptibility | journal = The Journal of Antimicrobial Chemotherapy | volume = 40 | issue = 1 | pages = 135–6 | date = July 1997 | pmid = 9249217 | doi = 10.1093/jac/40.1.135 | doi-access = free }} but the first case of S. aureus truly resistant to glycopeptide antibiotics was only reported in 2002.{{cite journal | vauthors = Chang S, Sievert DM, Hageman JC, Boulton ML, Tenover FC, Downes FP, Shah S, Rudrik JT, Pupp GR, Brown WJ, Cardo D, Fridkin SK | title = Infection with vancomycin-resistant Staphylococcus aureus containing the vanA resistance gene | journal = The New England Journal of Medicine | volume = 348 | issue = 14 | pages = 1342–7 | date = April 2003 | pmid = 12672861 | doi = 10.1056/NEJMoa025025 | doi-access = free }} Three cases of VRSA infection had been reported in the United States as of 2005.{{cite journal | vauthors = Menichetti F | title = Current and emerging serious Gram-positive infections | journal = Clinical Microbiology and Infection | volume = 11 | issue = Suppl 3 | pages = 22–28 | date = May 2005 | pmid = 15811021 | doi = 10.1111/j.1469-0691.2005.01138.x | doi-access = free }} At least in part the antimicrobial resistance in S. aureus can be explained by its ability to adapt. Multiple two component signal transduction pathways helps S. aureus to express genes that are required to survive under antimicrobial stress.{{cite journal | vauthors = Sengupta M, Jain V, Wilkinson BJ, Jayaswal RK | title = Chromatin immunoprecipitation identifies genes under direct VraSR regulation in Staphylococcus aureus | journal = Canadian Journal of Microbiology | volume = 58 | issue = 6 | pages = 703–8 | date = June 2012 | pmid = 22571705 | doi = 10.1139/w2012-043 }}

Among the various mechanisms that MRSA acquires to elude antibiotic resistance (e.g., drug inactivation, target alteration, reduction of permeability) there is also the overexpression of efflux pumps. Efflux pumps are membrane-integrated proteins that are physiologically needed in the cell for the exportation of xenobiotic compounds. They are divided into six families, each of which has a different structure, function, and transport of energy. The main efflux pumps of S. aureus are the MFS (Major Facilitator Superfamily) which includes the MdeA pump as well as the NorA pump and the MATE (Multidrug and Toxin Extrusion) to which it belongs the MepA pump. For transport, these families use an electrochemical potential and an ion concentration gradient, while the ATP-binding cassette (ABC) family acquires its energy from the hydrolysis of ATP.{{citation needed|date=December 2022}}

These pumps are overexpressed by MDR S. aureus (Multidrug resistant S. aureus) and the result is an excessive expulsion of the antibiotic outside the cell, which makes its action ineffective. Efflux pumps also contribute significantly to the development of impenetrable biofilms.{{citation needed|date=December 2022}}

By directly modulating efflux pumps' activity or decreasing their expression, it may be possible to modify the resistant phenotype and restore the effectiveness of existing antibiotics.{{cite journal | vauthors = Holasová K, Křížkovská B, Hoang L, Dobiasová S, Lipov J, Macek T, Křen V, Valentová K, Ruml T, Viktorová J | title = Flavonolignans from silymarin modulate antibiotic resistance and virulence in Staphylococcus aureus | journal = Biomedicine & Pharmacotherapy | volume = 149 | pages = 112806 | date = May 2022 | pmid = 35303568 | doi = 10.1016/j.biopha.2022.112806 | doi-access = free }}

About 33% of the U.S. population are carriers of S. aureus and about 2% carry MRSA.{{cite web|title=General Information: Community acquired MRSA|url=https://www.cdc.gov/mrsa/community/index.html|publisher=CDC|date=25 March 2016}} Even healthcare providers can be MRSA colonizers.{{cite journal | vauthors = Latha T, Bhat, Hande M, Mukhopadyay C, Devi ES, Nayak B | title = Methicillin-resistant staphylococcus aureus carriage among health-care professionals of a tertiary care hospital. | journal = Asian J Pharm Clin Res | date = 2018 | volume = 11 | issue = 3 | pages = 346–9 | doi = 10.22159/ajpcr.2018.v11i3.23151 | doi-access = free }}

The carriage of S. aureus is an important source of hospital-acquired infection (also called nosocomial) and community-acquired MRSA. Although S. aureus can be present on the skin of the host, a large proportion of its carriage is through the anterior nares of the nasal passages and can further be present in the ears.{{cite journal | vauthors = Campos A, Arias A, Betancor L, Rodríguez C, Hernández AM, López Aguado D, Sierra A | title = Study of common aerobic flora of human cerumen | journal = The Journal of Laryngology and Otology | volume = 112 | issue = 7 | pages = 613–6 | date = July 1998 | pmid = 9775288 | doi = 10.1017/s002221510014126x | s2cid = 29362695 }} The ability of the nasal passages to harbour S. aureus results from a combination of a weakened or defective host immunity and the bacterium's ability to evade host innate immunity.{{cite journal | vauthors = Quinn GA, Cole AM | title = Suppression of innate immunity by a nasal carriage strain of Staphylococcus aureus increases its colonization on nasal epithelium | journal = Immunology | volume = 122 | issue = 1 | pages = 80–89 | date = September 2007 | pmid = 17472720 | pmc = 2265977 | doi = 10.1111/j.1365-2567.2007.02615.x }} Nasal carriage is also implicated in the occurrence of staph infections.{{cite journal | vauthors = Wertheim HF, Melles DC, Vos MC, van Leeuwen W, van Belkum A, Verbrugh HA, Nouwen JL | title = The role of nasal carriage in Staphylococcus aureus infections | journal = The Lancet. Infectious Diseases | volume = 5 | issue = 12 | pages = 751–762 | date = December 2005 | pmid = 16310147 | doi = 10.1016/S1473-3099(05)70295-4 }}

Environmental contamination is thought to play a relatively less important part compared to direct transmission.{{cite journal | vauthors = Munir MT, Pailhories H, Eveillard M, Irle M, Aviat F, Federighi M, Belloncle C | title = Experimental Parameters Influence the Observed Antimicrobial Response of Oak Wood (Quercus petraea) | journal = Antibiotics | volume = 9 | issue = 9 | pages = 535 | date = August 2020 | pmid = 32847132 | pmc = 7558063 | doi = 10.3390/antibiotics9090535 | doi-access = free }} Emphasis on basic hand washing techniques are, therefore, effective in preventing its transmission. The use of disposable aprons and gloves by staff reduces skin-to-skin contact, so further reduces the risk of transmission.{{Cite web |title=CDC Media Relations: Press Release |url=https://www.cdc.gov/media/pressrel/fs021025.htm |access-date=2024-03-22 |website=www.cdc.gov}}

Recently,{{when|date=August 2023}} myriad cases of S. aureus have been reported in hospitals across America. Transmission of the pathogen is facilitated in medical settings where healthcare worker hygiene is insufficient. S. aureus is an incredibly hardy bacterium, as was shown in a study where it survived on polyester for just under three months;{{cite journal | vauthors = Neely AN, Maley MP | title = Survival of enterococci and staphylococci on hospital fabrics and plastic | journal = Journal of Clinical Microbiology | volume = 38 | issue = 2 | pages = 724–6 | date = February 2000 | pmid = 10655374 | pmc = 86187 | doi = 10.1128/JCM.38.2.724-726.2000 }} polyester is the main material used in hospital privacy curtains.

An important and previously unrecognized means of community-associated MRSA colonization and transmission is during sexual contact.{{cite journal | vauthors = Cook HA, Furuya EY, Larson E, Vasquez G, Lowy FD | title = Heterosexual transmission of community-associated methicillin-resistant Staphylococcus aureus | journal = Clinical Infectious Diseases | volume = 44 | issue = 3 | pages = 410–3 | date = February 2007 | pmid = 17205449 | doi = 10.1086/510681 | doi-access = free }}

Staphylococcus aureus is killed in one minute at 78 °C and in ten minutes at 64 °C but is resistant to freezing.{{cite journal |vauthors=Shafiei Y, Razavilar V, Javadi A |title=Thermal Death Time of Staphylococcus Aureus (PTCC=29213) and Staphylococcus Epidermidis (PTCC=1435) in Distilled Water |journal=Australian Journal of Basic and Applied Sciences |volume=5 |issue=11 |pages=1551–4 |year=2011 |url=http://ajbasweb.com/old/ajbas/2011/November-2011/1551-1554.pdf |archive-url=https://web.archive.org/web/20150702023512/http://ajbasweb.com/old/ajbas/2011/November-2011/1551-1554.pdf |archive-date=2015-07-02 |url-status=live }}{{cite journal | vauthors = Wu X, Su YC | title = Effects of frozen storage on survival of Staphylococcus aureus and enterotoxin production in precooked tuna meat | journal = Journal of Food Science | volume = 79 | issue = 8 | pages = M1554–M1559 | date = August 2014 | pmid = 25039601 | doi = 10.1111/1750-3841.12530 }}

Certain strains of S. aureus have been described as being resistant to chlorine disinfection.{{cite journal|title=Chlorine resistance of strains of Staphylococcus aureus isolated from poultry processing plants|journal=Letters in Applied Microbiology|volume=6|issue=2|pages=31–34|doi=10.1111/j.1472-765X.1988.tb01208.x|year=1988 | vauthors = Bolton KJ, Dodd CE, Mead GC, Waites WM |s2cid=84137649}}{{cite journal|title=Chlorine resistance of Staphylococcus aureus isolated from turkeys and turkey products|journal=Letters in Applied Microbiology|volume=3|issue=6|pages=131–3|doi=10.1111/j.1472-765X.1986.tb01566.x|year=1986 | vauthors = Mead GC, Adams BW |s2cid=86676949}}

The use of mupirocin ointment can reduce the rate of infections due to nasal carriage of S. aureus.{{cite journal | vauthors = van Rijen M, Bonten M, Wenzel R, Kluytmans J | title = Mupirocin ointment for preventing Staphylococcus aureus infections in nasal carriers | journal = The Cochrane Database of Systematic Reviews | issue = 4 | pages = CD006216 | date = October 2008 | volume = 2011 | pmid = 18843708 | doi = 10.1002/14651858.CD006216.pub2 | pmc = 8988859 | collaboration = Cochrane Wounds Group }} There is limited evidence that nasal decontamination of S. aureus using antibiotics or antiseptics can reduce the rates of surgical site infections.{{cite journal | vauthors = Liu Z, Norman G, Iheozor-Ejiofor Z, Wong JK, Crosbie EJ, Wilson P | title = Nasal decontamination for the prevention of surgical site infection in Staphylococcus aureus carriers | journal = The Cochrane Database of Systematic Reviews | volume = 5 | issue = 8 | pages = CD012462 | date = May 2017 | pmid = 28516472 | pmc = 6481881 | doi = 10.1002/14651858.CD012462.pub2 | collaboration = Cochrane Wounds Group }}

As of 2024, no approved vaccine exists against S. aureus. Early clinical trials have been conducted for several vaccines candidates such as Nabi's StaphVax and PentaStaph, Intercell's / Merck's V710, VRi's SA75, and others.{{cite web|url=http://www.rff.org/files/sharepoint/WorkImages/Download/ETC-07.pdf |archive-url=https://web.archive.org/web/20160308211758/http://www.rff.org/files/sharepoint/WorkImages/Download/ETC-07.pdf |archive-date=2016-03-08 |url-status=live |title=A Shot Against MRSA?|publisher=Resources for the Future |date=20 April 2009 |access-date=7 October 2015}}

While some of these vaccines candidates have shown immune responses, others aggravated an infection by S. aureus. To date, none of these candidates provides protection against a S. aureus infection. The development of Nabi's StaphVax was stopped in 2005 after phase III trials failed.{{cite web|url=http://www.formatex.info/microbiology4/vol3/1911-1925.pdf |archive-url=https://web.archive.org/web/20151122163352/http://www.formatex.info/microbiology4/vol3/1911-1925.pdf |archive-date=2015-11-22 |url-status=live |title=Strengthening the immune system as an antimicrobial strategy against Staphylococcus aureus infections |publisher=FORMATEX RESEARCH CENTER |date=11 December 2013 |access-date=7 October 2015}} Intercell's first V710 vaccine variant was terminated during phase II/III after higher mortality and morbidity were observed among patients who developed S. aureus infection.{{cite web|url=http://www.news-medical.net/news/20110608/Intercell-Merck-terminate-V710-Phase-IIIII-trial-against-S-aureus-infection.aspx |title=Intercell, Merck terminate V710 Phase II/III trial against S. aureus infection|publisher=Merck & Co. |date=8 June 2011 |access-date=7 October 2015}}

Nabi's enhanced S. aureus vaccines candidate PentaStaph was sold in 2011 to GlaxoSmithKline Biologicals S.A.{{cite press release|url=http://globenewswire.com/news-release/2011/04/27/445328/219830/en/Nabi-Biopharmaceuticals-Completes-Final-PentaStaph-TM-Milestone.html |title=Nabi Biopharmaceuticals Completes Final PentaStaph(TM) Milestone |publisher=GLOBE NEWSWIRE |date=27 April 2011 |access-date=7 October 2015}} The current status of PentaStaph is unclear. A WHO document indicates that PentaStaph failed in the phase III trial stage.{{cite web|url=https://www.who.int/immunization/research/forums_and_initiatives/4_OSchneewind_Staphylococcal_Vaccines_gvirf16.pdf |archive-url=https://web.archive.org/web/20160910053922/http://www.who.int/immunization/research/forums_and_initiatives/4_OSchneewind_Staphylococcal_Vaccines_gvirf16.pdf |archive-date=2016-09-10 |url-status=live |title=Vaccines to prevent antibiotic-resistant Staphylococcus aureus (MRSA)infections |publisher=University of Chicago |access-date=11 May 2017}}

In 2010, GlaxoSmithKline started a phase 1 blind study to evaluate its GSK2392103A vaccine.{{ClinicalTrialsGov|NCT01160172|A Study to Evaluate the Safety, Reactogenicity and Immunogenicity of GSK Biologicals' Staphylococcal Investigational Vaccine in Healthy Adults}} As of 2016, this vaccine is no longer under active development.{{cite web|url=http://www.nitag-resource.org/uploads/media/default/0001/03/041907310233c1d351cdc87ec952f56bd3abbed5.pdf |archive-url=https://web.archive.org/web/20161011140244/http://www.nitag-resource.org/uploads/media/default/0001/03/041907310233c1d351cdc87ec952f56bd3abbed5.pdf |archive-date=2016-10-11 |url-status=live |title=Status of vaccine research and development of vaccines for Staphylococcus aureus |publisher=Elsevier |date=19 April 2016 |access-date=10 October 2016}}

Pfizer's S. aureus four-antigen vaccine SA4Ag was granted fast track designation by the U.S. Food and Drug Administration in February 2014.{{cite web|url=http://www.pfizer.com/news/press-release/press-release-detail/pfizer_begins_phase_2b_study_of_its_investigational_multi_antigen_staphylococcus_aureus_vaccine_in_adults_undergoing_elective_spinal_fusion_surgery |title=Pfizer Begins Phase 2b Study of Its Investigational Multi-antigen Staphylococcus aureus Vaccine in Adults Undergoing Elective Spinal Fusion Surgery |publisher=Pfizer Inc. |date=7 July 2015 |access-date=24 February 2016}} In 2015, Pfizer has commenced a phase 2b trial regarding the SA4Ag vaccine.{{ClinicalTrialsGov|NCT02388165|Safety and Efficacy of SA4Ag Vaccine in Adults Having Elective Posterior Instrumented Lumbar Spinal Fusion Procedure (STRIVE)}} Phase 1 results published in February 2017 showed a very robust and secure immunogenicity of SA4Ag.{{cite journal | vauthors = Begier E, Seiden DJ, Patton M, Zito E, Severs J, Cooper D, Eiden J, Gruber WC, Jansen KU, Anderson AS, Gurtman A | title = SA4Ag, a 4-antigen Staphylococcus aureus vaccine, rapidly induces high levels of bacteria-killing antibodies | journal = Vaccine | volume = 35 | issue = 8 | pages = 1132–9 | date = February 2017 | pmid = 28143674 | doi = 10.1016/j.vaccine.2017.01.024 | doi-access = free }} The vaccine underwent clinical trial until June 2019, with results published in September 2020, that did not demonstrate a significant reduction in Postoperative Bloodstream Infection after Surgery.

In 2015, Novartis Vaccines and Diagnostics, a former division of Novartis and now part of GlaxoSmithKline, published promising pre-clinical results of their four-component Staphylococcus aureus vaccine, 4C-staph.{{cite journal | vauthors = Torre A, Bacconi M, Sammicheli C, Galletti B, Laera D, Fontana MR, Grandi G, De Gregorio E, Bagnoli F, Nuti S, Bertholet S, Bensi G | title = Four-component Staphylococcus aureus vaccine 4C-staph enhances Fcγ receptor expression in neutrophils and monocytes and mitigates S. aureus infection in neutropenic mice | journal = Infection and Immunity | volume = 83 | issue = 8 | pages = 3157–63 | date = August 2015 | pmid = 26015481 | pmc = 4496606 | doi = 10.1128/IAI.00258-15 }}

In addition to vaccine development, research is being performed to develop alternative treatment options that are effective against antibiotic resistant strains including MRSA. Examples of alternative treatments are phage therapy, antimicrobial peptides and host-directed therapy.{{cite journal | vauthors = Scheper H, Wubbolts JM, Verhagen JA, de Visser AW, van der Wal RJ, Visser LG, de Boer MG, Nibbering PH | title = SAAP-148 Eradicates MRSA Persisters Within Mature Biofilm Models Simulating Prosthetic Joint Infection | journal = Frontiers in Microbiology | volume = 12 | pages = 625952 | date = 2021-01-29 | pmid = 33584628 | pmc = 7879538 | doi = 10.3389/fmicb.2021.625952 | doi-access = free }}{{cite journal | vauthors = van den Biggelaar RH, Walburg KV, van den Eeden SJ, van Doorn CL, Meiler E, de Ries AS, Meijer AH, Ottenhoff TH, Saris A | title = Identification of kinase modulators as host-directed therapeutics against intracellular methicillin-resistant Staphylococcus aureus | journal = Frontiers in Cellular and Infection Microbiology | volume = 14 | pages = 1367938 | date = 2024 | pmid = 38590439 | pmc = 10999543 | doi = 10.3389/fcimb.2024.1367938 | doi-access = free }}

A number of standard strains of S. aureus (called "type cultures") are used in research and in laboratory testing, such as:

• Bundaberg tragedy, deaths of 12 children inoculated with an S. aureus-contaminated vaccine

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• {{cite journal | vauthors = Loskill P, Pereira PM, Jung P, Bischoff M, Herrmann M, Pinho MG, Jacobs K | title = Reduction of the peptidoglycan crosslinking causes a decrease in stiffness of the Staphylococcus aureus cell envelope | journal = Biophysical Journal | volume = 107 | issue = 5 | pages = 1082–9 | date = September 2014 | pmid = 25185544 | pmc = 4156677 | doi = 10.1016/j.bpj.2014.07.029 | bibcode = 2014BpJ...107.1082L }}
• {{cite journal | vauthors = Benson MA, Ohneck EA, Ryan C, Alonzo F, Smith H, Narechania A, Kolokotronis SO, Satola SW, Uhlemann AC, Sebra R, Deikus G, Shopsin B, Planet PJ, Torres VJ | title = Evolution of hypervirulence by a MRSA clone through acquisition of a transposable element | journal = Molecular Microbiology | volume = 93 | issue = 4 | pages = 664–681 | date = August 2014 | pmid = 24962815 | pmc = 4127135 | doi = 10.1111/mmi.12682 }}

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{{Medical resources

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{{Commons|Staphylococcus aureus}}

{{Wikispecies}}

• [http://www.stopmrsanow.org StopMRSANow.org] — Discusses how to prevent the spread of MRSA
• [http://www.themrsa.com TheMRSA.com] — Understand what the MRSA infection is all about.
• {{cite web |title=Staphylococcus aureus |work=NCBI Taxonomy Browser |url=https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=1280 |id=1280}}
• {{cite news|url = http://www.communities.gov.uk/publications/localgovernment/publictoiletsresponse|archive-url = http://webarchive.nationalarchives.gov.uk/20120919132719/http://www.communities.gov.uk/publications/localgovernment/publictoiletsresponse|url-status = dead|archive-date = 19 September 2012|title = Successful in vivo test of breakthrough Staphylococcus aureus vaccine| vauthors = Packham C |date = 16 March 2015|work = Medical Press|access-date =18 March 2015}}
• [http://bacdive.dsmz.de/index.php?search=14487&submit=Search Type strain of Staphylococcus aureus at BacDive – the Bacterial Diversity Metadatabase]

{{Gram-positive bacterial diseases}}

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Category:Food microbiology

aureus

Category:Bacteriology

Category:Gram-positive bacteria

Category:Bacterial diseases

Category:Pathogenic bacteria

Category:Healthcare-associated infections

Category:Bacteria described in 1884