Enterococcus faecalis

E. faecalis is a nonmotile microbe; it ferments glucose without gas production, and does not produce a catalase reaction with hydrogen peroxide. It produces a reduction of litmus milk, but does not liquefy gelatin. It shows consistent growth throughout nutrient broth which is consistent with being a facultative anaerobe. It catabolizes a variety of energy sources, including glycerol, lactate, malate, citrate, arginine, agmatine, and many keto acids. Enterococci survive very harsh environments, including extremely alkaline pH (9.6) and salt concentrations. They resist bile salts, detergents, heavy metals, ethanol, azide, and desiccation. They can grow in the range of 10 to 45 °C and survive at temperatures of 60 °C for 30 min.

E. faecalis is found in most healthy individuals, but can cause endocarditis and sepsis, urinary tract infections (UTIs), meningitis, and other infections in humans.{{cite journal | vauthors = Murray BE | title = The life and times of the Enterococcus | journal = Clinical Microbiology Reviews | volume = 3 | issue = 1 | pages = 46–65 | date = January 1990 | pmid = 2404568 | pmc = 358140 | doi = 10.1128/cmr.3.1.46 }}{{cite journal | vauthors = Hidron AI, Edwards JR, Patel J, Horan TC, Sievert DM, Pollock DA, Fridkin SK | title = NHSN annual update: antimicrobial-resistant pathogens associated with healthcare-associated infections: annual summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2006-2007 | journal = Infection Control and Hospital Epidemiology | volume = 29 | issue = 11 | pages = 996–1011 | date = November 2008 | pmid = 18947320 | doi = 10.1086/591861 | s2cid = 205988392 | author8 = National Healthcare Safety Network Team | author9 = Participating National Healthcare Safety Network Facilities }} Several virulence factors are thought to contribute to E. faecalis infections. A plasmid-encoded hemolysin, called the cytolysin, is important for pathogenesis in animal models of infection, and the cytolysin in combination with high-level gentamicin resistance is associated with a five-fold increase in risk of death in human bacteremia patients.{{cite journal | vauthors = Huycke MM, Spiegel CA, Gilmore MS | title = Bacteremia caused by hemolytic, high-level gentamicin-resistant Enterococcus faecalis | journal = Antimicrobial Agents and Chemotherapy | volume = 35 | issue = 8 | pages = 1626–1634 | date = August 1991 | pmid = 1929336 | pmc = 245231 | doi = 10.1128/aac.35.8.1626 }}{{cite journal | vauthors = Chow JW, Thal LA, Perri MB, Vazquez JA, Donabedian SM, Clewell DB, Zervos MJ | title = Plasmid-associated hemolysin and aggregation substance production contribute to virulence in experimental enterococcal endocarditis | journal = Antimicrobial Agents and Chemotherapy | volume = 37 | issue = 11 | pages = 2474–2477 | date = November 1993 | pmid = 8285637 | pmc = 192412 | doi = 10.1128/aac.37.11.2474 }}{{cite journal | vauthors = Ike Y, Hashimoto H, Clewell DB | title = Hemolysin of Streptococcus faecalis subspecies zymogenes contributes to virulence in mice | journal = Infection and Immunity | volume = 45 | issue = 2 | pages = 528–530 | date = August 1984 | pmid = 6086531 | pmc = 263283 | doi = 10.1128/IAI.45.2.528-530.1984 }} A plasmid-encoded adhesin{{cite journal | vauthors = Kreft B, Marre R, Schramm U, Wirth R | title = Aggregation substance of Enterococcus faecalis mediates adhesion to cultured renal tubular cells | journal = Infection and Immunity | volume = 60 | issue = 1 | pages = 25–30 | date = January 1992 | pmid = 1729187 | pmc = 257498 | doi = 10.1128/IAI.60.1.25-30.1992 }} called "aggregation substance" is also important for virulence in animal models of infection.{{cite journal | vauthors = Hirt H, Schlievert PM, Dunny GM | title = In vivo induction of virulence and antibiotic resistance transfer in Enterococcus faecalis mediated by the sex pheromone-sensing system of pCF10 | journal = Infection and Immunity | volume = 70 | issue = 2 | pages = 716–723 | date = February 2002 | pmid = 11796604 | pmc = 127697 | doi = 10.1128/iai.70.2.716-723.2002 }}

E. faecalis contains a tyrosine decarboxylase enzyme capable of decarboxylating L-DOPA, a crucial drug in the treatment of Parkinson's disease. If L-DOPA is decarboxylated in the gut microbiome, it cannot pass through the blood-brain barrier and be decarboxylated in the brain to become dopamine.{{cite journal | vauthors = Maini Rekdal V, Bess EN, Bisanz JE, Turnbaugh PJ, Balskus EP | title = Discovery and inhibition of an interspecies gut bacterial pathway for Levodopa metabolism | journal = Science | volume = 364 | issue = 6445 | pages = eaau6323 | date = June 2019 | pmid = 31196984 | pmc = 7745125 | doi = 10.1126/science.aau6323 }}

File:Enterococcus faecalis.jpg

{{Main|Vancomycin-resistant Enterococcus}}

E. faecalis is usually resistant to many commonly used antimicrobial agents (aminoglycosides, aztreonam and quinolones). The resistance is mediated by the presence of multiple genes related to drug resistance in the chromosome or plasmid.

Resistance to vancomycin in E. faecalis is becoming more common.{{cite journal | vauthors = Amyes SG | title = Enterococci and streptococci | journal = International Journal of Antimicrobial Agents | volume = 29 | issue = Suppl 3 | pages = S43–S52 | date = May 2007 | pmid = 17659211 | doi = 10.1016/S0924-8579(07)72177-5 }}{{cite journal | vauthors = Courvalin P | title = Vancomycin resistance in gram-positive cocci | journal = Clinical Infectious Diseases | volume = 42 | issue = Suppl 1 | pages = S25–S34 | date = January 2006 | pmid = 16323116 | doi = 10.1086/491711 | doi-access = free }} Treatment options for vancomycin-resistant E. faecalis include nitrofurantoin (in the case of uncomplicated UTIs),{{cite journal | vauthors = Zhanel GG, Hoban DJ, Karlowsky JA | title = Nitrofurantoin is active against vancomycin-resistant enterococci | journal = Antimicrobial Agents and Chemotherapy | volume = 45 | issue = 1 | pages = 324–326 | date = January 2001 | pmid = 11120989 | pmc = 90284 | doi = 10.1128/AAC.45.1.324-326.2001 }} linezolid, quinupristin, tigecycline and daptomycin, although ampicillin is preferred if the bacteria are susceptible.{{cite journal | vauthors = Arias CA, Contreras GA, Murray BE | title = Management of multidrug-resistant enterococcal infections | journal = Clinical Microbiology and Infection | volume = 16 | issue = 6 | pages = 555–562 | date = June 2010 | pmid = 20569266 | pmc = 3686902 | doi = 10.1111/j.1469-0691.2010.03214.x }} Quinupristin/dalfopristin can be used to treat Enterococcus faecium but not E. faecalis.

In root-canal treatments, NaOCl and chlorhexidine (CHX) are used to fight E. faecalis before isolating the canal. However, recent studies determined that NaOCl or CHX showed low ability to eliminate E. faecalis.{{cite journal | vauthors = Estrela C, Silva JA, de Alencar AH, Leles CR, Decurcio DA | title = Efficacy of sodium hypochlorite and chlorhexidine against Enterococcus faecalis--a systematic review | journal = Journal of Applied Oral Science | volume = 16 | issue = 6 | pages = 364–368 | date = December 2008 | pmid = 19082392 | pmc = 4327704 | doi = 10.1590/s1678-77572008000600002 }}

{{Expand section|date=January 2019}}{{Main|Enterococcus#Antibacterial resistance}}

According to one study combined drug therapy has shown some efficacy in cases of severe infections (e.g. heart valves infections) against susceptible strains of E. faecalis. Ampicillin- and vancomycin-sensitive E. faecalis (lacking high-level resistance to aminoglycosides) strains can be treated by gentamicin and ampicillin antibiotics. A less nephrotoxic combination of ampicillin and ceftriaxone (even though E. faecalis is resistant to cephalosporins, ceftriaxone is working synergistically with ampicillin) may be used alternatively for ampicillin-susceptible E. faecalis.{{cite journal | vauthors = Dubin K, Pamer EG | title = Enterococci and Their Interactions with the Intestinal Microbiome | journal = Microbiology Spectrum | volume = 5 | issue = 6 | pages = 309–330 | date = November 2014 | pmid = 29125098 | pmc = 5691600 | doi = 10.1128/microbiolspec.BAD-0014-2016 | isbn = 978-1-55581-969-9 | veditors = Britton RA, Cani PD }}

Daptomycin or linezolid may also show efficacy in case ampicillin and vancomycin resistance.

A combination of penicillin and streptomycin therapy was used in the past.

Tedizolid, telavancin, dalbavancin, and oritavancin antibiotics are FDA approved as treatments against EF.{{cite journal | vauthors = Singh H, Das S, Yadav J, Srivastava VK, Jyoti A, Kaushik S | title = In search of novel protein drug targets for treatment of Enterococcus faecalis infections | journal = Chemical Biology & Drug Design | volume = 94 | issue = 4 | pages = 1721–1739 | date = October 2019 | pmid = 31260188 | doi = 10.1111/cbdd.13582 | publisher = Wiley | s2cid = 195756723 }}

UTIs are among the most common bacterial infections and their treatment is becoming increasingly challenging due to the rise of multidrug-resistant E. faecalis strains. Current UTI treatments rely mainly on antibiotics. One promising alternative is the combination of bacteriophage therapy and β-lactam antibiotics. This approach is known as phage-antibiotic synergy (PAS), it has been shown to enhance bacterial elimination, improve biofilm penetration, reduce the emergence of resistant mutants and increase bacterial susceptibility to antibiotics.

There have been many promising studies about phage-antibiotic synergy with different pathogens such as Pseudomonas aeruginosa or Staphylococcus aureus. With E. faecalis there have been fewer studies, but promising results from a recent study by Moryl et al. (2024) demonstrated that the combination on phage therapy and β-lactam antibiotics enhanced treatment outcomes (more efficient bacteria elimination and increased bacterial sensitivity to antibiotics) and decreased resistance development.

More research is still needed to identify optimal phage-antibiotic combinations and treatment protocols, but this could potentially be considered a possible alternative treatment for antibiotic-resistant E. faecalis infections in the future.

• Endures prolonged periods of nutritional deprivation
• Binds to dentin and proficiently spreads into dentinal tubules via chain propagation
• Alters host responses
• Suppresses the action of lymphocytes
• Possesses lytic enzymes, cytolysin, aggregation substance, pheromones, and lipoteichoic acid
• Utilizes serum as a nutritional source
• Produces extracellular superoxide under selected growth conditions that can generate chromosomal instability in mammalian cells{{cite journal | vauthors = Huycke MM, Moore D, Joyce W, Wise P, Shepard L, Kotake Y, Gilmore MS | title = Extracellular superoxide production by Enterococcus faecalis requires demethylmenaquinone and is attenuated by functional terminal quinol oxidases | journal = Molecular Microbiology | volume = 42 | issue = 3 | pages = 729–740 | date = November 2001 | pmid = 11722738 | doi = 10.1046/j.1365-2958.2001.02638.x | s2cid = 25075356 | doi-access = }}{{cite journal | vauthors = Wang X, Huycke MM | title = Extracellular superoxide production by Enterococcus faecalis promotes chromosomal instability in mammalian cells | journal = Gastroenterology | volume = 132 | issue = 2 | pages = 551–561 | date = February 2007 | pmid = 17258726 | doi = 10.1053/j.gastro.2006.11.040 | doi-access = free }}
• Resists intracanal medicaments (e.g. calcium hydroxide), although a study proposes elimination from root canals after using a mixture of a tetracycline isomer, an acid, and a detergent{{cite journal | vauthors = Shabahang S, Pouresmail M, Torabinejad M | title = In vitro antimicrobial efficacy of MTAD and sodium hypochlorite | journal = Journal of Endodontics | volume = 29 | issue = 7 | pages = 450–452 | date = July 2003 | pmid = 12877261 | doi = 10.1097/00004770-200307000-00006 }}
• Maintains pH homeostasis
• Properties of dentin lessen the effect of calcium hydroxide
• Competes with other cells
• Forms a biofilm{{cite journal | vauthors = Stuart CH, Schwartz SA, Beeson TJ, Owatz CB | title = Enterococcus faecalis: its role in root canal treatment failure and current concepts in retreatment | journal = Journal of Endodontics | volume = 32 | issue = 2 | pages = 93–98 | date = February 2006 | pmid = 16427453 | doi = 10.1016/j.joen.2005.10.049 | url = https://zenodo.org/record/1259157 }}
• Activates the host protease plasminogen in a fashion that increases local tissue destruction{{cite journal | vauthors = Jacobson RA, Wienholts K, Williamson AJ, Gaines S, Hyoju S, van Goor H, Zaborin A, Shogan BD, Zaborina O, Alverdy JC | title = Enterococcus faecalis exploits the human fibrinolytic system to drive excess collagenolysis: implications in gut healing and identification of druggable targets | journal = American Journal of Physiology. Gastrointestinal and Liver Physiology | volume = 318 | issue = 1 | pages = G1–G9 | date = January 2020 | pmid = 31604031 | pmc = 6985841 | doi = 10.1152/ajpgi.00236.2019 }}

In human blood, E. faecalis is subjected to conditions that damage its DNA, but this damage can be tolerated by the use of DNA repair processes.{{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 | date = November 2020 | pmid = 33203752 | pmc = 7683395 | doi = 10.1128/mBio.02288-20 }} This damage tolerance depends, in part, on the two protein complex RexAB, encoded by the E. faecalis genome, that is employed in the recombinational repair of DNA double-strand breaks.

The ability of E. faecalis to form biofilms contributes to its capacity to survive in extreme environments, and facilitates its involvement in persistent bacterial infection, particularly in the case of multi-drug resistant strains.{{cite journal |vauthors=Șchiopu P, Toc DA, Colosi IA, Costache C, Ruospo G, Berar G, Gălbău ȘG, Ghilea AC, Botan A, Pană AG, Neculicioiu VS, Todea DA |title=An Overview of the Factors Involved in Biofilm Production by the Enterococcus Genus |journal=Int J Mol Sci |volume=24 |issue=14 |date=July 2023 |page=11577 |pmid=37511337 |pmc=10380289 |doi=10.3390/ijms241411577 |doi-access=free |url=}} Biofilm formation in E. faecalis is associated with DNA release, and such release has emerged as a fundamental aspect of biofilm formation. Conjugative plasmid DNA transfer in E. faecalis is enhanced by the release of peptide sex pheromones.{{cite journal |vauthors=Hirt H, Greenwood-Quaintance KE, Karau MJ, Till LM, Kashyap PC, Patel R, Dunny GM |title=Enterococcus faecalis Sex Pheromone cCF10 Enhances Conjugative Plasmid Transfer In Vivo |journal=mBio |volume=9 |issue=1 |pages= |date=February 2018 |pmid=29440568 |pmc=5821081 |doi=10.1128/mBio.00037-18 |url=}}

Prior to 1984, enterococci were members of the genus Streptococcus; thus, E. faecalis was known as Streptococcus faecalis.{{cite journal | vauthors = Schleifer KH, Kilpper-Balz R |title=Transfer of Streptococcus faecalis and Streptococcus faecium to the Genus Enterococcus nom. rev. as Enterococcus faecalis comb. nov. and Enterococcus faecium comb. nov. |journal=International Journal of Systematic Bacteriology |date=1 January 1984 |volume=34 |issue=1 |pages=31–34 |doi=10.1099/00207713-34-1-31 |doi-access=free }}

In 2013, a combination of cold denaturation and NMR spectroscopy was used to show detailed insights into the unfolding of the E. faecalis homodimeric repressor protein CylR2.{{cite journal | vauthors = Jaremko M, Jaremko Ł, Kim HY, Cho MK, Schwieters CD, Giller K, Becker S, Zweckstetter M | title = Cold denaturation of a protein dimer monitored at atomic resolution | journal = Nature Chemical Biology | volume = 9 | issue = 4 | pages = 264–270 | date = April 2013 | pmid = 23396077 | pmc = 5521822 | doi = 10.1038/nchembio.1181 }}

The E. faecalis genome consists of 3.22 million base pairs with 3,113 protein-coding genes.{{cite journal | vauthors = Paulsen IT, Banerjei L, Myers GS, Nelson KE, Seshadri R, Read TD, Fouts DE, Eisen JA, Gill SR, Heidelberg JF, Tettelin H, Dodson RJ, Umayam L, Brinkac L, Beanan M, Daugherty S, DeBoy RT, Durkin S, Kolonay J, Madupu R, Nelson W, Vamathevan J, Tran B, Upton J, Hansen T, Shetty J, Khouri H, Utterback T, Radune D, Ketchum KA, Dougherty BA, Fraser CM | title = Role of mobile DNA in the evolution of vancomycin-resistant Enterococcus faecalis | journal = Science | volume = 299 | issue = 5615 | pages = 2071–2074 | date = March 2003 | pmid = 12663927 | doi = 10.1126/science.1080613 | s2cid = 45480495 | bibcode = 2003Sci...299.2071P }}

Glutamate racemase, hydroxymethylglutaryl-CoA synthase, diphosphomevalonate decarboxylase, topoisomerase DNA gyrase B, D-alanine—D-serine ligase, alanine racemase, phosphate acetyltransferase, NADH peroxidase,Phosphopantetheine adenylyltransferase (PPAT), acyl carrier protein, 3‐Dehydroquinate dehydratase and Deoxynucleotide triphosphate triphosphohydrolase are all potential molecules that may be used for treating EF infections.

Bacillus haynesii CD223 and Advenella mimigardefordensis SM421 can inhibit the growth of Enterococcus faecalis.{{cite journal | vauthors = Rahman MM, Paul SI, Rahman A, Haque MS, Ador MA, Foysal MJ, Islam MT, Rahman MM | title = Suppression of Streptococcosis and Modulation of the Gut Bacteriome in Nile Tilapia (Oreochromis niloticus) by the Marine Sediment Bacteria Bacillus haynesii and Advenella mimigardefordensis | journal = Microbiology Spectrum | volume = 10 | issue = 6 | pages = e0254222 | date = December 2022 | pmid = 36453920 | pmc = 9769507 | doi = 10.1128/spectrum.02542-22 | veditors = Rogovskyy AS, Weththasinghe P, Rodriguez-Estrada U }}

Bacterial small RNAs play important roles in many cellular processes; 11 small RNAs have been experimentally characterised in E. faecalis V583 and detected in various growth phases.{{cite journal | vauthors = Shioya K, Michaux C, Kuenne C, Hain T, Verneuil N, Budin-Verneuil A, Hartsch T, Hartke A, Giard JC | title = Genome-wide identification of small RNAs in the opportunistic pathogen Enterococcus faecalis V583 | journal = PLOS ONE | volume = 6 | issue = 9 | pages = e23948 | date = 2 September 2011 | pmid = 21912655 | pmc = 3166299 | doi = 10.1371/journal.pone.0023948 | doi-access = free | bibcode = 2011PLoSO...623948S }} Five of them have been shown to be involved in stress response and virulence.{{cite journal | vauthors = Michaux C, Hartke A, Martini C, Reiss S, Albrecht D, Budin-Verneuil A, Sanguinetti M, Engelmann S, Hain T, Verneuil N, Giard JC | title = Involvement of Enterococcus faecalis small RNAs in stress response and virulence | journal = Infection and Immunity | volume = 82 | issue = 9 | pages = 3599–3611 | date = September 2014 | pmid = 24914223 | pmc = 4187846 | doi = 10.1128/IAI.01900-14 }}

A genome-wide sRNA study suggested that some sRNAs are linked to the antibiotic resistance and stress response in another Enterococcus: E. faecium.{{cite journal | vauthors = Sinel C, Augagneur Y, Sassi M, Bronsard J, Cacaci M, Guérin F, Sanguinetti M, Meignen P, Cattoir V, Felden B | title = Small RNAs in vancomycin-resistant Enterococcus faecium involved in daptomycin response and resistance | journal = Scientific Reports | volume = 7 | issue = 1 | pages = 11067 | date = September 2017 | pmid = 28894187 | pmc = 5593968 | doi = 10.1038/s41598-017-11265-2 | bibcode = 2017NatSR...711067S }}

Because E. faecalis is a common fecal bacterium in humans, recreational water facilities (such as swimming pools and beaches that allow visitors to swim in the ocean) often measure the concentrations of E. faecalis to assess the quality of their water. The higher the concentration, the worse the quality of the water. The practice of using E. faecalis as a quality indicator is recommended by the World Health Organization (WHO) as well as many developed countries after multiple studies have reported that higher concentrations of E. faecalis correlate to greater percentages of swimmer illness. This correlation exists in both freshwater and marine environments, so measuring E. faecalis concentrations to determine water quality applies to all recreational waters. However, the correlation does not imply that E. faecalis is the ultimate cause of swimmer illnesses. One alternative explanation is that higher levels of E. faecalis correspond to higher levels of human viruses, which cause sickness in swimmers. Although this claim may sound plausible, there is currently little evidence that establishes the link between E. faecalis and human virus (or other pathogens) levels. Thus, despite the strong correlation between E. faecalis and water quality, more research is needed to determine the causal relationship of this correlation.{{Citation | vauthors = Boehm AB, Sassoubre LM |title=Enterococci as Indicators of Environmental Fecal Contamination |date=2014 |url=http://www.ncbi.nlm.nih.gov/books/NBK190421/ |work=Enterococci: From Commensals to Leading Causes of Drug Resistant Infection | veditors = Gilmore MS, Clewell DB, Ike Y, Shankar N |access-date=2023-05-08 |place=Boston |publisher=Massachusetts Eye and Ear Infirmary |pmid=24649503 }}

For recreational waters near or at beaches, E. faecalis can come from multiple sources, such as the sand and human bodies. Determining the sources of E. faecalis is crucial for controlling water contamination, though often the sources are non-point (for example, human bathers). As such, one study looked at how much E. faecalis is shed from bathers at the beach. The first group of participants immersed themselves in a large pool with marine water for 4 cycles of 15 minutes, both with and without contacting sand beforehand. The result shows a decrease in E. faecalis levels for each cycle, suggesting that people shed the most bacteria when they first get into a pool. The second group of participants entered small, individual pools after contact with beach sand, and researchers collected data on how much E. faecalis in the pool came from the sand brought by the participants and how much came from the participants’ shedding. The result shows that E. faecalis from the sand is very small compared to that from human shedding. Although this result may not apply to all sand types, a tentative conclusion is that human shedding is a major non-point source of E. faecalis in recreational waters.{{cite journal | vauthors = Elmir SM, Wright ME, Abdelzaher A, Solo-Gabriele HM, Fleming LE, Miller G, Rybolowik M, Peter Shih MT, Pillai SP, Cooper JA, Quaye EA | title = Quantitative evaluation of bacteria released by bathers in a marine water | journal = Water Research | volume = 41 | issue = 1 | pages = 3–10 | date = January 2007 | pmid = 17113123 | pmc = 2633726 | doi = 10.1016/j.watres.2006.10.005 | bibcode = 2007WatRe..41....3E }}

• Anti-Q RNA

{{Reflist}}

{{Commons category}}

• [http://bacdive.dsmz.de/index.php?search=5292&submit=Search Type strain of Enterococcus faecalis at BacDive – the Bacterial Diversity Metadatabase]

{{Gram-positive bacterial diseases}}

{{Taxonbar|from=Q140014}}

{{Authority control}}

faecalis

Category:Bacteria described in 1906