cross-resistance

Cross-resistance is the idea is that the development of resistance to one substance subsequently leads to resistance to one or more substances that can be resisted in a similar manner. It occurs when resistance is provided against multiple compounds through one single mechanism, like an efflux pump.{{cite book |doi=10.1016/bs.ampbs.2017.02.001 |chapter=Metal Resistance and Its Association with Antibiotic Resistance |title=Microbiology of Metal Ions |series=Advances in Microbial Physiology |date=2017 |last1=Pal |first1=Chandan |last2=Asiani |first2=Karishma |last3=Arya |first3=Sankalp |last4=Rensing |first4=Christopher |last5=Stekel |first5=Dov J. |last6=Larsson |first6=D.G. Joakim |last7=Hobman |first7=Jon L. |volume=70 |pages=261–313 |pmid=28528649 |isbn=978-0-12-812386-7 }} This can keep concentrations of a toxic substance at low levels and can do so for multiple compounds. Increasing the activity of such a mechanism in response to one compound then also has a similar effect on the others. The precise definition of cross-resistance depends on the field of interest.

In pest management, cross-resistance is defined as the development of resistance by pest populations to multiple pesticides within a chemical family.{{cite book |doi=10.1016/b978-0-12-818654-1.00023-2 |chapter=New advances in insect vector biology and virus epidemiology |title=Applied Plant Virology |date=2020 |last1=Sarwar |first1=Muhammad |last2=Aslam |first2=Roohi |pages=301–311 |isbn=978-0-12-818654-1 }} Similar to the case of microbes, this may occur due to sharing binding target sites. For example, cadherin mutations may result in cross resistance in H. armigera to Cry1Aa and Cry1Ab. There also exists multiple resistance in which resistance to multiple pesticides occurs via different resistance mechanisms as opposed to the same mechanisms.{{cite book |doi=10.1016/B978-0-12-800197-4.00006-3 |chapter=Detection and Mechanisms of Resistance Evolved in Insects to Cry Toxins from Bacillus thuringiensis |title=Insect Midgut and Insecticidal Proteins |series=Advances in Insect Physiology |date=2014 |last1=Wu |first1=Yidong |volume=47 |pages=297–342 |isbn=978-0-12-800197-4 }}

In another case it is defined as the resistance of a virus to a new drug as a result of previous exposure to another drug.{{cite journal |last1=Locarnini |first1=Stephen |last2=Bowden |first2=Scott |title=Drug Resistance in Antiviral Therapy |journal=Clinics in Liver Disease |date=August 2010 |volume=14 |issue=3 |pages=439–459 |doi=10.1016/j.cld.2010.05.004 |pmid=20638024 }} Or in the context of microbes, it is the resistance to multiple different antimicrobial agents as a result of a single molecular mechanism.{{cite journal |last1=Colclough |first1=Abigail |last2=Corander |first2=Jukka |last3=Sheppard |first3=Samuel K. |last4=Bayliss |first4=Sion C. |last5=Vos |first5=Michiel |title=Patterns of cross-resistance and collateral sensitivity between clinical antibiotics and natural antimicrobials |journal=Evolutionary Applications |date=June 2019 |volume=12 |issue=5 |pages=878–887 |doi=10.1111/eva.12762 |pmc=6503891 |pmid=31080502 |bibcode=2019EvApp..12..878C }}

Cross-resistance is highly involved in the widespread issue of antibiotic resistance; an area of clinical relevance. There is a continued increase in the development of multidrug resistance in bacteria. This is partially due to the widespread use of antimicrobial compounds in diverse environments.{{cite journal |last1=Anes |first1=João |last2=McCusker |first2=Matthew P. |last3=Fanning |first3=Séamus |last4=Martins |first4=Marta |title=The ins and outs of RND efflux pumps in Escherichia coli |journal=Frontiers in Microbiology |date=10 June 2015 |volume=6 |page=587 |doi=10.3389/fmicb.2015.00587 |pmid=26113845 |pmc=4462101 |doi-access=free }} But resistance to antibiotics can arise in multiple ways, not necessarily being the result of exposure to an antimicrobial compound.

Cross-resistance can take place between compounds that are chemically similar, like antibiotics within similar and different classes.{{cite journal |last1=Sanders |first1=C C |last2=Sanders |first2=W E |last3=Goering |first3=R V |last4=Werner |first4=V |title=Selection of multiple antibiotic resistance by quinolones, beta-lactams, and aminoglycosides with special reference to cross-resistance between unrelated drug classes |journal=Antimicrobial Agents and Chemotherapy |date=December 1984 |volume=26 |issue=6 |pages=797–801 |doi=10.1128/AAC.26.6.797 |pmid=6098219 |pmc=180026 }} That said, structural similarity is a weak predictor of antibiotic resistance, and does not predict antibiotic resistance at all when aminoglycosides are disregarded in the comparison.{{Cite journal |last1=Lázár |first1=Viktória |last2=Nagy |first2=István |last3=Spohn |first3=Réka |last4=Csörgő |first4=Bálint |last5=Györkei |first5=Ádám |last6=Nyerges |first6=Ákos |last7=Horváth |first7=Balázs |last8=Vörös |first8=Andrea |last9=Busa-Fekete |first9=Róbert |last10=Hrtyan |first10=Mónika |last11=Bogos |first11=Balázs |last12=Méhi |first12=Orsolya |last13=Fekete |first13=Gergely |last14=Szappanos |first14=Balázs |last15=Kégl |first15=Balázs |title=Genome-wide analysis captures the determinants of the antibiotic cross-resistance interaction network |journal=Nature Communications |year=2014 |language=en |volume=5 |page=4352 |doi=10.1038/ncomms5352 |pmid=25000950|pmc=4102323 |bibcode=2014NatCo...5.4352L }}

Cross resistance will most commonly occur due to target similarity. This is possible when antimicrobial agents have the same target, initiate cell death in a similar manner or have a similar route of access. An example is cross-resistance between antibiotics and disinfectants. Exposure to certain disinfectants can lead to the increased expression of genes that encode for efflux pumps that are able to maintain low levels of antibiotics. Thus, the same mechanism that is used to clear the disinfectant compound from the cell can also be used to clear antibiotics from the cell.{{cite journal |last1=Chapman |first1=John S. |title=Disinfectant resistance mechanisms, cross-resistance, and co-resistance |journal=International Biodeterioration & Biodegradation |date=June 2003 |volume=51 |issue=4 |pages=271–276 |doi=10.1016/s0964-8305(03)00044-1 |bibcode=2003IBiBi..51..271C }} Another example is cross-resistance between antibiotics and metals. As mentioned before, compounds do not have to be similar in structure in order to lead to cross-resistance. It can also occur when the same mechanism is used to remove the compound from the cell. In the bacteria Listeria monocytogenes a multi-drug efflux transporter has been found that could export both metals and antibiotics.{{cite journal | last1=Mata | first1=M.T. | last2=Baquero | first2=F. | last3=Pérez-Díaz | first3=J.C. | title=A multidrug efflux transporter in Listeria monocytogenes | journal=FEMS Microbiology Letters | volume=187 | issue=2 | year=2000 | doi=10.1111/j.1574-6968.2000.tb09158.x | pages=185–188| pmid=10856655 | doi-access=free }}{{cite journal |last1=Baker-Austin |first1=Craig |last2=Wright |first2=Meredith S. |last3=Stepanauskas |first3=Ramunas |last4=McArthur |first4=J.V. |title=Co-selection of antibiotic and metal resistance |journal=Trends in Microbiology |date=April 2006 |volume=14 |issue=4 |pages=176–182 |doi=10.1016/j.tim.2006.02.006 |pmid=16537105 }} Experimental work has shown that exposure to zinc can lead to increased levels of bacterial resistance to antibiotics.{{cite journal |last1=Peltier |first1=Edward |last2=Vincent |first2=Joshua |last3=Finn |first3=Christopher |last4=Graham |first4=David W. |title=Zinc-induced antibiotic resistance in activated sludge bioreactors |journal=Water Research |date=July 2010 |volume=44 |issue=13 |pages=3829–3836 |doi=10.1016/j.watres.2010.04.041 |pmid=20537675 |bibcode=2010WatRe..44.3829P }} Several other studies have reported cross-resistance to various types of metals and antibiotics. These worked through several mechanisms, like drug efflux systems and disulphide bond formation systems. The possible implication of this is that not only the presence of antibacterial compounds can lead to the development of resistance against antibiotics, but also environmental factors like exposure to heavy metals.

Collateral sensitivity is a phenomenon where resistance to a drug leads to increased susceptibility to another drug. This concept has been studied in both bacteria{{Cite journal |last1=Aulin |first1=Linda B. S. |last2=Liakopoulos |first2=Apostolos |last3=van der Graaf |first3=Piet H. |last4=Rozen |first4=Daniel E. |last5=van Hasselt |first5=J. G. Coen |date=2021-09-28 |title=Design principles of collateral sensitivity-based dosing strategies |journal=Nature Communications |language=en |volume=12 |issue=1 |pages=5691 |doi=10.1038/s41467-021-25927-3 |pmc=8479078 |pmid=34584086|bibcode=2021NatCo..12.5691A }} and in pathogenic fungi{{Cite journal |last1=Carolus |first1=Hans |last2=Sofras |first2=Dimitrios |last3=Boccarella |first3=Giorgio |last4=Jacobs |first4=Stef |last5=Biriukov |first5=Vladislav |last6=Goossens |first6=Louise |last7=Chen |first7=Alicia |last8=Vantyghem |first8=Ina |last9=Verbeeck |first9=Tibo |last10=Pierson |first10=Siebe |last11=Lobo Romero |first11=Celia |last12=Steenackers |first12=Hans |last13=Lagrou |first13=Katrien |last14=van den Berg |first14=Pieter |last15=Berman |first15=Judith |date=November 2024 |title=Collateral sensitivity counteracts the evolution of antifungal drug resistance in Candida auris |journal=Nature Microbiology |language=en |volume=9 |issue=11 |pages=2954–2969 |doi=10.1038/s41564-024-01811-w |pmid=39472696 }} Researchers have discovered that collateral sensitivity-based treatments are effective against resistant populations in vitro, which is promising regarding the effort to combat the harms created by cross resistance to commonly used antibiotics.{{Cite journal |last1=Pál |first1=Csaba |last2=Papp |first2=Balázs |last3=Lázár |first3=Viktória |date=July 2015 |title=Collateral sensitivity of antibiotic-resistant microbes |journal=Trends in Microbiology |volume=23 |issue=7 |pages=401–407 |doi=10.1016/j.tim.2015.02.009 |pmc=5958998 |pmid=25818802}} Increased sensitivity to an antibiotic means that a lower concentration of antibiotic can be used to achieve adequate growth inhibition.

While the individual mechanisms for collateral sensitivity are not yet well-understood, it is thought that collateral sensitivity and antimicrobial resistance exist as a trade-off in which the benefits gained by antibiotic resistance are balanced by the risks introduced by collateral sensitivity.{{cite journal |last1=Roemhild |first1=Roderich |last2=Andersson |first2=Dan I. |title=Mechanisms and therapeutic potential of collateral sensitivity to antibiotics |journal=PLOS Pathogens |date=14 January 2021 |volume=17 |issue=1 |pages=e1009172 |doi=10.1371/journal.ppat.1009172 |pmc=7808580 |pmid=33444399 |doi-access=free}} A specific mechanism of antimicrobial resistance may reduce the organism's fitness, and therefore expose or increase its vulnerability to a different class of drug. As more research is conducted in this area collateral sensitivity based treatments could be utilised for known multidrug resistant pathogens, such as methicillin resistant Staphylococcus aureus, Candida auris and Candida albicans.{{fact|date=February 2025}}

• Drug resistance
• Pesticide resistance

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Category:Toxicology

Category:Pesticides

Category:Agricultural pests

Category:Evolutionary biology

Category:Antimicrobial resistance