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Disinfectants and antiseptics: mechanisms of action and resistance

Nature Reviews Microbiology volume 22, pages 4–17 (2024)Cite this article

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Abstract

Chemical biocides are used for the prevention and control of infection in health care, targeted home hygiene or controlling microbial contamination for various industrial processes including but not limited to food, water and petroleum. However, their use has substantially increased since the implementation of programmes to control outbreaks of methicillin-resistant Staphylococcus aureus, Clostridioides difficile and severe acute respiratory syndrome coronavirus 2. Biocides interact with multiple targets on the bacterial cells. The number of targets affected and the severity of damage will result in an irreversible bactericidal effect or a reversible bacteriostatic one. Most biocides primarily target the cytoplasmic membrane and enzymes, although the specific bactericidal mechanisms vary among different biocide chemistries. Inappropriate usage or low concentrations of a biocide may act as a stressor while not killing bacterial pathogens, potentially leading to antimicrobial resistance. Biocides can also promote the transfer of antimicrobial resistance genes. In this Review, we explore our current understanding of the mechanisms of action of biocides, the bacterial resistance mechanisms encompassing both intrinsic and acquired resistance and the influence of bacterial biofilms on resistance. We also consider the impact of bacteria that survive biocide exposure in environmental and clinical contexts.

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Fig. 1: Susceptibility of microorganisms to biocides.
Fig. 2: Mechanisms of action of disinfectants and antiseptics.
Fig. 3: Intrinsic factors governing microbial resistance and tolerance to biocides.

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References

  1. Fraise, A. in Principles and Practice of Disinfection, Preservation and Sterilization 5th edn (eds Fraise, A. P., Maillard, J.-Y. & Sattar, S.) 1–4 (Wiley-Blackwell, 2013).

  2. Pasteur, L. On the extension of the germ theory to the etiology of certain common diseases [French]. Comptes Rendus de l’Académie des Sciences XC, 1033–1044 (1880).

  3. Walker, L., Levine, H. & Jucker, M. Koch’s postulates and infectious proteins. Acta Neuropathol. 112, 1–4 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Carter, K. C. Ignaz Semmelweis, Carl Mayrhofer, and the rise of germ theory. Med. Hist. 29, 33–53 (1985).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Maillard, J.-Y. et al. Does microbicide use in consumer products promote antimicrobial resistance? A critical review and recommendations for a cohesive approach to risk assessment. Microb. Drug. Res. 19, 344–354 (2013). This opinion paper highlights the issues associated with a lack of definition of ‘biocide resistance’ and with a lack of consensus for measuring bacterial resistance to biocides.

    Article  Google Scholar 

  6. European Commission. Scientific Committee on Emerging and Newly Identified Health Risks (SCENIHR). Assessment of the Antibiotic Resistance Effects of Biocides. European Commission http://ec.europa.eu/health/ph_risk/committees/04_scenihr/docs/scenihr_o_021.pdf (2009).

  7. Mueller, S. & Beraud, S. S. L. The Biocides Market in the Times of Coronavirus. S&P Global Commodity Insights https://www.spglobal.com/commodityinsights/en/ci/research-analysis/the-biocides-market-in-the-times-of-coronavirus.html (2020).

  8. Maillard, J.-Y. Resistance of bacteria to biocides. Microbiol. Spectrum 6, ARBA-0006-2017 (2018).

    Article  Google Scholar 

  9. Ko, S., An, H. S., Bang, J. H. & Park, S. W. An outbreak of Burkholderia cepacia complex pseudobacteremia associated with intrinsically contaminated commercial 0.5% chlorhexidine solution. Am. J. Infect. Control 43, 266–268 (2015).

    Article  CAS  PubMed  Google Scholar 

  10. Nakashima, A. K., McCarthy, M. A., Martone, W. J. & Anderson, R. L. Epidemic septic arthritis caused by Serratia marcescens and associated with benzalkonium chloride antiseptic. J. Clin. Microbiol. 25, 1014–1018 (1987).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Hsueh, P.-R. et al. Nosocomial pseudoepidemic caused by Bacillus cereus traced to contaminated ethyl alcohol from a liquor factory. J. Clin. Microbiol. 37, 2280–2284 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Poole, K. Mechanisms of bacterial biocide and antibiotic resistance. J. Appl. Microbiol. 92, 55S–64S (2002).

    Article  PubMed  Google Scholar 

  13. Griffiths, P. A., Babb, J. R., Bradley, C. R. & Fraise, A. P. Glutaraldehyde resistant Mycobacterium chelonae from endoscope washer disinfectors. J. Appl. Microbiol. 82, 519–526 (1997).

    Article  CAS  PubMed  Google Scholar 

  14. Martin, D. J. H., Denyer, S. P., McDonnell, G. & Maillard, J.-Y. Resistance and cross-resistance to oxidising agents of bacterial isolates from endoscope washer disinfectors. J. Hosp. Infect. 69, 377–383 (2008). This paper presents evidence of vegetative bacteria isolated from an endoscope washer disinfector (using chlorine dioxide high-level disinfection), resistant to in-use concentration of chlorine dioxide and other reactive biocides.

    Article  CAS  PubMed  Google Scholar 

  15. Martin, D. J. H., Wesgate, R., Denyer, S. P., McDonnell, G. & Maillard, J.-Y. Bacillus subtilis vegetative isolate surviving chlorine dioxide exposure: an elusive mechanism of resistance. J. Appl. Microbiol. 119, 1541–1551 (2015).

    Article  CAS  PubMed  Google Scholar 

  16. Russell, A. D. Biocides — mechanisms of action and microbial resistance. World J. Microbiol. Biotechnol. 8, 58–59 (1992).

    Article  PubMed  Google Scholar 

  17. McDonnell, G. & Russell, A. D. Antiseptics and disinfectants: activity, action, and resistance. Clin. Microbiol. Rev. 12, 147–179 (1999). This review highlights the limitation of biocide efficacy depending on their chemistry and the propensity for microbial resistance resulting from exposure to a low concentration of a biocide.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Russell, A. D. Biocide use and antibiotic resistance: the relevance of laboratory findings to clinical and environmental situations. Lancet Infect. Dis. 3, 794–803 (2003).

    Article  CAS  PubMed  Google Scholar 

  19. Maillard, J.-Y. Impact of benzalkonium chloride, benzethonium chloride and chloroxylenol on bacterial resistance and cross-resistance to antimicrobials. J. Appl. Microbiol. 133, 3322–3346 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Wand, M. E. & Sutton, J. M. Efflux-mediated tolerance to cationic biocides, a cause for concern? Microbiology 168, 1263 (2022).

    Article  CAS  Google Scholar 

  21. Vijayakumar, R. & Sandle, T. A review on biocide reduced susceptibility due to plasmid-borne antiseptic-resistant genes — special notes ion pharmaceutical environmental isolates. J. Appl. Microbiol. 126, 1011–1022 (2019).

    Article  CAS  PubMed  Google Scholar 

  22. Jones, I. A. & Joshi, L. Biocide use in the antimicrobial era: a review. Molecules 26, 2276 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Al-Adham, I., Haddadin, R. & Collier, P. in Principles and Practice of Disinfection, Preservation and Sterilization 5th edn (eds Fraise, A. P., Maillard, J.-Y. & Sattar, S.) 5–70 (Wiley-Blackwell, 2013).

  24. Singer, A. C., Shaw, H., Rhodes, V. & Hart, A. Review of antimicrobial resistance in the environment and its relevance to environmental regulators. Front. Microbiol. 7, 1728 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  25. Leggett, M. J., Setlow, P., Sattar, S. A. & Maillard, J.-Y. Assessing the activity of microbicides against bacterial spores: knowledge and pitfalls. J. Appl. Microbiol. 120, 1174–1180 (2016).

    Article  CAS  PubMed  Google Scholar 

  26. Forbes, S. et al. Formulation of biocides increases antimicrobial potency and mitigates the enrichment of nonsusceptible bacteria in multispecies. Appl. Environ. Microbiol. 83, e3054-16 (2017).

    Article  Google Scholar 

  27. Maillard, J.-Y. Bacterial target sites for biocide action. J. Appl. Microbiol. 92, 16S–27S (2002).

    Article  PubMed  Google Scholar 

  28. Sani, M.-A. et al. Maculatin 1.1 disrupts Staphylococcus aureus lipid membranes via a pore mechanism. Antimicrob. Agents Chemother. 57, 3593–3600 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Johnston, M. D., Hanlon, G. W., Denyer, S. P. & Lambert, R. J. W. Membrane damage to bacteria caused by single and combined biocides. J. Appl. Microbiol. 94, 1015–1023 (2003).

    Article  CAS  PubMed  Google Scholar 

  30. Barros, A. C., Melo, L. F. & Pereira, A. A multi-purpose approach to the mechanisms of action of two biocides (benzalkonium chloride and dibromonitrilopropionamide): discussion of Pseudomonas fluorescens’ viability and death. Front. Microbiol. 13, 842414 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  31. Linley, E., Denyer, S. P., McDonnell, G., Simons, C. & Maillard, J.-Y. Use of hydrogen peroxide as a biocide: new consideration of its mechanisms of biocidal action. J. Antimicrob. Chemother. 67, 1589–1596 (2012).

    Article  CAS  PubMed  Google Scholar 

  32. Setlow, B., Atluri, S., Kitchel, R., Koziol-Dube, K. & Setlow, P. Role of dipicolinic acid in resistance and stability of spores of Bacillus subtilis with or without DNA-protective α/β-type small acid-soluble proteins. J. Bacteriol. 188, 3740–3747 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Leggett, M. J. et al. Resistance to and killing by the sporicidal microbicide peracetic acid. J. Antimicrob. Chemother. 70, 773–779 (2015).

    Article  CAS  PubMed  Google Scholar 

  34. Alkhalifa, S. et al. Analysis of the destabilization of bacterial membranes by quaternary ammonium compounds: a combined experimental and computational study. ChemBioChem 21, 1510–1516 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Bore, E. et al. Adapted tolerance to benzalkonium chloride in Escherichia coli K-12 studied by transcriptome and proteome analyses. Microbiology 153, 935–946 (2007).

    Article  CAS  PubMed  Google Scholar 

  36. Roth, M. et al. Transcriptomic analysis of E. coli after exposure to a sublethal concentration of hydrogen peroxide revealed a coordinated up-regulation of the cysteine biosynthesis pathway. Antioxidants 11, 655 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Denyer, S. P. & Maillard, J.-Y. Cellular impermeability and uptake of biocides and antibiotics in Gram-negative bacteria. J. Appl. Microbiol. 92, 35S–45S (2002).

    Article  PubMed  Google Scholar 

  38. Denyer, S. P. Mechanisms of action of biocides. Int. Biodeter. 26, 89–100 (1990).

    Article  CAS  Google Scholar 

  39. McMurry, L. M., Oethinger, M. & Levy, S. B. Triclosan targets lipid synthesis. Nature 394, 531–532 (1998).

    Article  CAS  PubMed  Google Scholar 

  40. Simões, L. C. et al. Persister cells in a biofilm treated with a biocide. Biofouling 27, 403–411 (2011).

    Article  PubMed  Google Scholar 

  41. Fernandes, S., Gomes, I. B., Sousa, S. F. & Simões, M. Antimicrobial susceptibility of persister biofilm cells of Bacillus cereus and Pseudomonas fluorescens. Microorganisms 10, 160 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Maillard, J.-Y. Usage of antimicrobial biocides and products in the healthcare environment: efficacy, policies, management and perceived problems. Ther. Clin. Risk Manag. 1, 340–370 (2005).

    Google Scholar 

  43. Russell, A. D. & McDonnell, G. Concentration: a major factor in studying biocidal action. J. Hosp. Infect. 44, 1–3 (2000).

    Article  CAS  PubMed  Google Scholar 

  44. Lambert, P. A. Cellular impermeability and uptake of biocides and antibiotics in Gram-positive bacteria and mycobacteria. J. Appl. Microbiol. 92, 46S–54S (2002).

    Article  PubMed  Google Scholar 

  45. Lambert, R. J. W., Hanlon, G. W. & Denyer, S. P. The synergistic effect of EDTA/antimicrobial combinations on Pseudomonas aeruginosa. J. Appl. Microbiol. 96, 244–253 (2004).

    Article  CAS  PubMed  Google Scholar 

  46. Leggett, M. J., McDonnell, G., Denyer, S. P., Setlow, P. & Maillard, J.-Y. Bacterial spore structures and their protective role in biocide resistance. J. Appl. Microbiol. 113, 485–498 (2012).

    Article  CAS  PubMed  Google Scholar 

  47. Maillard, J.-Y. Innate resistance to sporicides and potential failure to decontaminate. J. Hosp. Infect. 77, 204–209 (2011).

    Article  PubMed  Google Scholar 

  48. Vickery, K. et al. Presence of biofilm containing viable multiresistant organisms despite terminal cleaning on clinical surfaces in an intensive care unit. J. Hosp. Infect. 80, 52–55 (2012).

    Article  CAS  PubMed  Google Scholar 

  49. Hu, H. et al. Intensive care unit environmental surfaces are contaminated by multidrug-resistant bacteria in biofilms: combined results of conventional culture, pyrosequencing, scanning electron microscopy, and confocal laser microscopy. J. Hosp. Infect. 91, 35–44 (2015).

    Article  CAS  PubMed  Google Scholar 

  50. Ledwoch, K. et al. Beware biofilm! Dry biofilms containing bacterial pathogens on multiple healthcare surfaces; a multi-centre study. J. Hosp. Infect. 100, E47–E56 (2018).

    Article  CAS  PubMed  Google Scholar 

  51. Ledwoch, K. et al. Is a reduction in viability enough to determine biofilm susceptibility to a biocide? Infect. Control. Hosp. Epidemiol. 42, 1486–1492 (2021).

    Article  PubMed  Google Scholar 

  52. Bridier, A., Dubois-Brissonnet, F., Greub, G., Thomas, V. & Briandet, R. Dynamics of the action of biocides in Pseudomonas aeruginosa biofilms. Antimicrob. Agents Chemother. 55, 2648–2654 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Stewart, P. S. Antimicrobial tolerance in biofilms. Microbiol. Spectr. https://doi.org/10.1128/microbiolspec.MB-0010-2014 (2015).

    Article  PubMed  Google Scholar 

  54. Bas, S., Kramer, M. & Stopar, D. Biofilm surface density determines biocide effectiveness. Front. Microbiol. 8, 2443 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  55. Araújo, P. A., Mergulhão, F., Melo, L. & Simões, M. The ability of an antimicrobial agent to penetrate a biofilm is not correlated with its killing or removal efficiency. Biofouling 30, 673–683 (2014).

    Article  Google Scholar 

  56. Wood, T. K., Knabel, S. J. & Kwana, B. W. Bacterial persister cell formation and dormancy. Appl. Environ. Microbiol. 79, 7116–7121 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Podlesek, Z. & Bertok, D. Z. The DNA damage inducible SOS response is a key player in the generation of bacterial persister cells and population wide tolerance. Front. Microbiol. 4, 1785 (2020).

    Article  Google Scholar 

  58. Ciusa, M. L. et al. A novel resistance mechanism to triclosan that suggests horizontal gene transfer and demonstrates a potential selective pressure for reduced biocide susceptibility in clinical strains of Staphylococcus aureus. Int. J. Antimicrob. Agents 40, 210–220 (2012).

    Article  CAS  PubMed  Google Scholar 

  59. Jia, Y., Lu, H. & Zhua, L. Molecular mechanism of antibiotic resistance induced by mono- and twin-chained quaternary ammonium compounds. Sci. Total Environ. 832, 155090 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Schindler, B. D. & Kaatz, G. W. Multidrug efflux pumps of Gram-positive bacteria. Drug Res. Updates 27, 1–13 (2016).

    Article  CAS  Google Scholar 

  61. Poole, K. Outer membranes and efflux: the path to multidrug resistance in Gram-negative bacteria. Curr. Pharm. Biotechnol. 3, 77–98 (2002).

    Article  CAS  PubMed  Google Scholar 

  62. Chitsaz, M. & Brown, M. H. The role played by drug efflux pumps in bacterial multidrug resistance. Essays Biochem. 61, 127–139 (2017).

    Article  PubMed  Google Scholar 

  63. Rajamohan, G., Srinivasan, V. B. & Gebreyes, W. A. Novel role of Acinetobacter baumannii RND efflux transporters in mediating decreased susceptibility to biocides. J. Antimicrob. Chemother. 65, 228–232 (2010).

    Article  CAS  PubMed  Google Scholar 

  64. LaBreck, P. T. et al. Systematic analysis of efflux pump-mediated antiseptic resistance in Staphylococcus aureus suggests a need for greater antiseptic stewardship. mSphere 5, e00959-19 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Wand, M. E., Darby, E. M., Blair, J. M. A. & Sutton, J. M. Contribution of the efflux pump AcrAB-TolC to the tolerance of chlorhexidine and other biocides in Klebsiella spp. J. Med. Microbiol. 71, 001496 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Fernández-Cuenca, F. et al. Reduced susceptibility to biocides in Acinetobacter baumannii: association with resistance to antimicrobials, epidemiological behaviour, biological cost and effect on the expression of genes encoding porins and efflux pumps. J. Antimicrob. Chemother. 70, 3222–3229 (2015).

    Article  PubMed  Google Scholar 

  67. Kim, M. et al. Widely used benzalkonium chloride disinfectants can promote antibiotic resistance. Appl. Environ. Microbiol. 84, 1201–1218 (2018).

    Article  Google Scholar 

  68. Nordholt, N., Kanaris, O., Schmidt, S. B. I. & Schreiber, F. Persistence against benzalkonium chloride promotes rapid evolution of tolerance during periodic disinfection. Nat. Commun. 12, 6792 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Amsalu, A. et al. Efflux pump-driven antibiotic and biocide cross-resistance in Pseudomonas aeruginosa isolated from different ecological niches: a case study in the development of multidrug resistance in environmental hotspots. Microorganisms 8, 1647 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Sánchez, M. B. et al. Predictive studies suggest that the risk for the selection of antibiotic resistance by biocides is likely low in Stenotrophomonas maltophilia. PLoS ONE 10, e0132816 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  71. Bay, D. C. & Turner, R. J. Diversity and evolution of the small multidrug resistance protein family. BMC Evol. Biol. 9, 140 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  72. Hansen, L. S., Jensen, L. B., Sørensen, H. I. & Sørensen, S. J. Substrate specificity of the OqxAB multidrug resistance pump in Escherichia coli and selected enteric bacteria. J. Antimicrob. Chemother. 60, 145–147 (2007).

    Article  CAS  PubMed  Google Scholar 

  73. Kaatz, G. W. & Seo, S. M. Effect of substrate exposure and other growth condition manipulations on norA expression. J. Antimicrob. Chemother. 54, 364–369 (2004).

    Article  CAS  PubMed  Google Scholar 

  74. Mima, T., Joshi, S., Gomez-Escalada, M. & Schweizer, H. P. Identification and characterization of TriABC-OpmH, a triclosan efflux pump of Pseudomonas aeruginosa requiring two membrane fusion proteins. J. Bacteriol. 189, 7600–7609 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Buffet-Bataillon, S., Tattevin, P., Maillard, J.-Y., Bonnaure-Mallet, M. & Jolivet-Gougeon, A. Efflux pump induction by quaternary ammonium compounds and fluoroquinolone resistance in bacteria. Future Microbiol. 11, 81–92 (2016).

    Article  CAS  PubMed  Google Scholar 

  76. Reza, A., Sutton, J. M. & Rahman, K. M. Effectiveness of efflux pump inhibitors as biofilm disruptors and resistance breakers in Gram-negative (ESKAPEE) bacteria. Antibiotics 8, 229 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Kvist, M., Hancok, V. & Klemm, O. P. Inactivation if efflux pumps abolishes bacterial biofilm formation. Appl. Environ. Microbiol. 74, 7376–7382 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Soto, S. M. Role of efflux pumps in the antibiotic resistance of bacteria embedded in a biofilm. Virulence 4, 223–229 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  79. Chevalier, S. et al. Structure function and regulation of Pseudomonas aeruginosa porins. FEMS Microbiol. Rev. 41, 698–772 (2017).

    Article  CAS  PubMed  Google Scholar 

  80. Svetlíková, Z. et al. Role of porins in the susceptibility of Mycobacterium smegmatis and Mycobacterium chelonae to aldehyde-based disinfectants and drugs. Antimicrob. Agents Chemother. 53, 4015–4018 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  81. Stahl, C. et al. MspA provides the main hydrophilic pathway through the cell wall of Mycobacterium smegmatis. Mol. Microbiol. 40, 451–464 (2001).

    Article  CAS  PubMed  Google Scholar 

  82. Pereira, B. M. P., Wang, X. K. & Tagkopoulos, I. Biocide-induced emergence of antibiotic resistance in Escherichia coli. Front. Microbiol. 12, 640923 (2021).

    Article  Google Scholar 

  83. Silver, S. Bacterial silver resistance: molecular biology and uses and misuse of silver compounds. FEMS Microbiol. Rev. 27, 341–353 (2003).

    Article  CAS  PubMed  Google Scholar 

  84. Casado Muñoz, M. C. et al. Comparative proteomic analysis of a potentially probiotic Lactobacillus pentosus MP-10 for the identification of key proteins involved in antibiotic resistance and biocide tolerance. Int. J. Food Microbiol. 222, 8–15 (2016).

    Article  PubMed  Google Scholar 

  85. Allen, M. J., White, G. F. & Morby, A. P. The response of Escherichia coli to exposure to the biocide polyhexamethylene biguanide. Microbiology 152, 989–1000 (2006).

    Article  CAS  PubMed  Google Scholar 

  86. Motgatla, R. M., Gouws, P. A. & Brözel, V. S. Mechanisms contributing to hypochlorous acid resistance of a Salmonella isolate from a poultry-processing plant. J. Appl. Microbiol. 92, 566–573 (2002).

    Article  Google Scholar 

  87. Wu, C. H. A review of microbial injury and recovery methods in food. Food Microbiol. 25, 735–744 (2008).

    Article  CAS  PubMed  Google Scholar 

  88. Yildiz, F. H. & Schoolnik, G. K. Vibrio cholerae O1 E1 Tor: identification of a gene cluster required for the rugose colony type, exopolysaccharide production, chlorine resistance and biofilm formation. Proc. Natl Acad. Sci. USA 96, 4028–4033 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Koska, M. et al. Distinct long- and short-term adaptive mechanisms in Pseudomonas aeruginosa. Microbiol. Spectr. 10, e0304322 (2022).

    Article  PubMed  Google Scholar 

  90. Keim, K. C., George, I. K., Reynolds, L. & Smith, A. C. The clinical significance of Staphylococcus aureus small colony variants. Lab. Med. 54, 227–234 (2023).

    Article  PubMed  Google Scholar 

  91. Seaman, P. F., Ochs, D. & Day, M. J. Small-colony variants: a novel mechanism for triclosan resistance in methicillin-resistant Staphylococcus aureus. J. Antimicrob. Chemother. 59, 43–450 (2007).

    Article  CAS  PubMed  Google Scholar 

  92. Pitton, M. et al. Mutation to ispA produces stable small-colony variants of Pseudomonas aeruginosa that have enhanced aminoglycoside resistance. Antimicrob. Agents Chemother. 66, e0062122 (2022).

    Article  PubMed  Google Scholar 

  93. Zhou, S., Rao, Y., Li, J., Huang, Q. & Rao, X. Staphylococcus aureus small-colony variants: formation, infection, and treatment. Microbiol. Res. 260, 127040 (2022).

    Article  CAS  PubMed  Google Scholar 

  94. Fischer, A. J. Small colonies, bigger problems? New evidence that Staphylococcus aureus small colony variants can worsen lung inflammation in cystic fibrosis rats. Infect. Immun. 90, e0041322 (2022).

    Article  PubMed  Google Scholar 

  95. McNamara, P. J. & Proctor, R. A. Staphylococcus aureus small colony variants, electron transport and persistent infections. Int. J. Antimicrob. Agents 14, 117–122 (2000).

    Article  CAS  PubMed  Google Scholar 

  96. Gilman, S. & Saunders, V. A. Accumulation of gentamicin by Staphylococcus aureus: the role of the transmembrane electrical potential. J. Antimicrob. Chemother. 17, 37–44 (1986).

    Article  CAS  PubMed  Google Scholar 

  97. Guo, H. et al. Biofilm and small colony variants — an update on Staphylococcus aureus strategies toward drug resistance. Int. J. Mol. Sci. 23, 1241 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Wesgate, R., Fanning, S., Hu, Y. & Maillard, J.-Y. The effect of exposure to microbicide residues at ‘during use’ concentrations on antimicrobial susceptibility profile, efflux, conjugative plasmid transfer and metabolism of Escherichia coli. Antimicrob. Agents Chemother. 64, e01131-20 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Bischofberger, A. M., Baumgartner, M., Pfrunder-Cardozo, K. R., Allen, R. C. & Hall, A. R. Associations between sensitivity to antibiotics, disinfectants and heavy metals in natural, clinical and laboratory isolates of Escherichia coli. Environ. Microbiol. 22, 2664–2679 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Webber, M. A., Coldham, N. G., Woodward, M. J. & Piddock, L. J. V. Proteomic analysis of triclosan resistance in Salmonella enterica serovar Typhimurium. J. Antimicrob. Chemother. 62, 92–97 (2008).

    Article  CAS  PubMed  Google Scholar 

  101. Condell, O. et al. Comparative analysis of Salmonella susceptibility and tolerance to the biocide chlorhexidine identifies a complex cellular defense network. Front. Microbiol. 5, 373 (2014). This paper identifies the expression of multiple mechanisms in response to biocide exposure, reporting for the first time, to our knowledge, a complex cellular defence network and emphasizing that bacterial response to biocide stress does rely on a combination of mechanisms.

    Article  PubMed  PubMed Central  Google Scholar 

  102. Curiao, T. et al. Multiple adaptive routes of Salmonella enterica Typhimurium to biocide and antibiotic exposure. BMC Genomics 17, 491 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  103. Pi, B. R., Yu, D. L., Hua, X. T., Ruan, Z. & Yu, Y. S. Genomic and transcriptome analysis of triclosan response of a multidrug-resistant Acinetobacter baumannii strain, MDR-ZJ06. Arch. Microbiol. 199, 223–230 (2017).

    Article  CAS  PubMed  Google Scholar 

  104. Curiao, T. et al. Polymorphic variation in susceptibility and metabolism of triclosan-resistant mutants of Escherichia coli and Klebsiella pneumoniae clinical strains obtained after exposure to biocides and antibiotics. Antimicrob. Agents Chemother. 59, 3413–3423 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. McMurry, L. M., Oethinger, M. & Levy, S. B. Overexpression of marA, soxS, or acrAB produces resistance to triclosan in laboratory and clinical strains of Escherichia coli. FEMS Microbiol. Lett. 166, 305–309 (1998).

    Article  CAS  PubMed  Google Scholar 

  106. Bailey, A. M. et al. Exposure of Escherichia coli and serovar Typhimurium to triclosan induces a species-specific response, including drug detoxification. J. Antimicrob. Chemother. 64, 973–985 (2009).

    Article  CAS  PubMed  Google Scholar 

  107. Dejoies, L., Le Neindre, K., Reissier, S., Felden, B. & Cattoir, V. Distinct expression profiles of regulatory RNAs in the response to biocides in Staphylococcus aureus and Enterococcus faecium. Sci. Rep. 11, 6892 (2021). This paper documents the impact of biocide exposure at a subinhibitory concentration on the expression of small RNA (sRNA) in Staphylococcus aureus and Enterococcus faecium, demonstrating that sRNA-mediated responses were mostly repressed potentially leading to specific bacterial response and adaptation to biocides.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Demple, B. Redox signaling and gene control in the Escherichia coli soxRS oxidative stress regulon — a review. Gene 179, 53–57 (1996).

    Article  CAS  PubMed  Google Scholar 

  109. Koutsolioutsou, A., Pena-Llopis, S. & Demple, B. Constitutive soxR mutations contribute to multiple-antibiotic resistance in clinical Escherichia coli isolates. Antimicrob. Agents Chemother. 49, 2746–2752 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Wand, M. E., Bock, L. J., Bonney, L. C. & Sutton, J. M. Mechanisms of increased resistance to chlorhexidine and cross-resistance to colistin following exposure of Klebsiella pneumoniae clinical isolates to chlorhexidine. Antimicrob. Agents Chemother. 61, e01162-16 (2016).

    PubMed  PubMed Central  Google Scholar 

  111. Kastbjerg, V. G., Hein-Kristensen, L. & Gram, L. Triclosan-induced aminoglycoside-tolerant Listeria monocytogenes isolates can appear as small-colony variants. Antimicrob. Agents Chemother. 58, 3124–3132 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  112. McMurry, L. M., McDermott, P. F. & Levy, S. B. Genetic evidence that InhA of Mycobacterium smegmatis is a target for triclosan. Antimicrob. Agents Chemother. 43, 711–713 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. International Organization for Standardization. ISO: 20776-1. Clinical Laboratory Testing and In Vitro Diagnostic Test Systems: Susceptibility Testing of Infectious Agents and Evaluation of Performance of Antimicrobial Susceptibility Test Devices. Part 1. Reference Method for Testing the In Vitro Activity of Antimicrobial Agents Against Rapidly Growing Aerobic Bacteria Involved in Infectious Diseases (British Standard Institute, 2006).

  114. European Committee on Antimicrobial Susceptibility Testing (EUCAST). Breakpoint Tables for Interpretation of MICs and Zone Diameters. Version 4.0 (EUCAST, 2014).

  115. Andrews, J. M. BSAC Working Party on Susceptibility Testing. BSAC standardized disc susceptibility testing method (version 8). J. Antimicrob. Chemother. 64, 454–489 (2009).

    Article  CAS  PubMed  Google Scholar 

  116. Bock, L. J., Hind, C. K., Sutton, J. M. & Wand, M. E. Growth media and assay plate material can impact on the effectiveness of cationic biocides and antibiotics against different bacterial species. Lett. Appl. Microbiol. 66, 368–377 (2018).

    Article  CAS  PubMed  Google Scholar 

  117. Kampf, G. Suitability of methods to determine resistance to biocidal active substances and disinfectants — a systematic review. Hygiene 2, 109–119 (2022).

    Article  Google Scholar 

  118. Kahlmeter, G. et al. European harmonization of MIC breakpoints for antimicrobial susceptibility testing of bacteria. J. Antimicrob. Chemother. 52, 145–148 (2003).

    Article  CAS  PubMed  Google Scholar 

  119. Coelho et al. The use of machine learning methodologies to analyse antibiotic and biocide susceptibility in Staphylococcus aureus. PLoS ONE 8, e55582 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Walsh, S. E. et al. Development of bacterial resistance to several biocides and effects on antibiotic susceptibility. J. Hosp. Infect. 55, 98–107 (2003).

    Article  CAS  PubMed  Google Scholar 

  121. Alonso-Calleja, C., Guerrero-Ramos, E., Alonso-Hernando, A. & Capita, R. Adaptation and cross-adaptation of Escherichia coli ATCC 12806 to several food-grade biocides. Food Control 56, 86–94 (2015).

    Article  CAS  Google Scholar 

  122. Cowley, N. L. et al. Effects of formulation on microbicide potency and mitigation of the development of bacterial insusceptibility. Appl. Environ. Microbiol. 81, 7330–7338 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Wesgate, R., Grasha, P. & Maillard, J.-Y. Use of a predictive protocol to measure the antimicrobial resistance risks associated with biocidal product usage. Am. J. Infect. Control 44, 458–464 (2016).

    Article  CAS  PubMed  Google Scholar 

  124. Randall, L. P. et al. Commonly used farm disinfectants can select for mutant Salmonella enterica serovar Typhimurium with decreased susceptibility to biocides and antibiotics without compromising virulence. J. Antimicrob. Chemother. 60, 1273–1280 (2007).

    Article  CAS  PubMed  Google Scholar 

  125. Weber, D. J., Rutala, W. A. & Sickbert-Bennett, E. E. Outbreaks associated with contaminated antiseptics and disinfectants. Antimicrob. Agents Chemother. 51, 4217–4224 (2007). This review presents evidence of bacterial contamination of biocidal products and highlights the reasons for product failure, including contamination with an intrinsically resistant bacterium or spore, or product misuse.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Maillard, J.-Y. in Blocks’ Disinfection, Sterilization and Preservation 6th edn (eds McDonnell, G. & Hansen, J.) 44–67 (Wolters Kluwer, 2020).

  127. de Frutos, M. et al. Serratia marcescens outbreak due to contaminated 2% aqueous chlorhexidine. Enferm. Infecc. Microbiol. Clin. 35, 624–629 (2016).

    PubMed  Google Scholar 

  128. Anyiwo, C. E., Coker, A. O. & Daniel, S. O. Pseudomonas aeruginosa in postoperative wounds from chlorhexidine solutions. J. Hosp. Infect. 3, 189–191 (1982).

    Article  CAS  PubMed  Google Scholar 

  129. Wishart, M. M. & Riley, T. V. Infection with Pseudomonas maltophilia hospital outbreak due to contaminated disinfectant. Med. J. Aust. 2, 710–712 (1976).

    Article  CAS  PubMed  Google Scholar 

  130. Georgia Division of Public Health. Abscesses in an allergy practice due to Mycobacterium chelonae. Georgia Epidemiol. Rep. 6, 2 (1960).

    Google Scholar 

  131. Guinness, M. & Levey, J. Contamination of aqueous dilutions of Resiguard disinfectant with Pseudomonas. Med. J. Aust. 2, 392 (1976).

    Article  CAS  PubMed  Google Scholar 

  132. Cason, J. S., Jackson, D. M., Lowbury, E. J. & Ricketts, C. R. Antiseptic and septic prophylaxis for burns: use of silver nitrate and of isolators. Br. Med. J. 2, 1288–1294 (1966).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Duarte, R. S. et al. Epidemic of postsurgical infections caused by Mycobacterium massiliense. J. Clin. Microbiol. 47, 2149–2155 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  134. Ben Miloud, S., Ali, M. M., Boutiba, I., Van Houdt, R. & Chouchani, C. First report of cross resistance to silver and antibiotics in Klebsiella pneumoniae isolated from patients and polluted water in Tunisia. Water Environ. J. 35, 730–739 (2021).

    Article  Google Scholar 

  135. Molina-González, D., Alonso-Calleja, C., Alonso-Hernando, A. & Capita, R. Effect of sub-lethal concentrations of biocides on the susceptibility to antibiotics of multi-drug resistant Salmonella enterica strains. Food Control 40, 329–334 (2014).

    Article  Google Scholar 

  136. Amos, G. C. A. et al. The widespread dissemination of integrons throughout bacterial communities in a riverine system. ISME J. 12, 681–691 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Randall, L. P. et al. Fitness and dissemination of disinfectant-selected multiple-antibiotic-resistant (MAR) strains of Salmonella enterica serovar Typhimurium in chickens. J. Antimicrob. Chemother. 61, 156–162 (2008).

    Article  CAS  PubMed  Google Scholar 

  138. Cole, E. C. et al. Investigation of antibiotic and antibacterial agent cross-resistance in target bacteria from homes of antibacterial product users and nonusers. J. Appl. Microbiol. 95, 664–676 (2003).

    Article  CAS  PubMed  Google Scholar 

  139. Carson, R. T., Larson, E., Levy, S. B., Marshall, B. M. & Aiello, A. E. Use of antibacterial consumer products containing quaternary ammonium compounds and drug resistance in the community. J. Antimicrob. Chemother. 62, 1160–1162 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Short, F. L. et al. Benzalkonium chloride antagonises aminoglycoside antibiotics and promotes evolution of resistance. eBioMedicine 73, 103653 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Liu, Q. et al. Frequency of biocide-resistant genes and susceptibility to chlorhexidine in high-level mupirocin-resistant, methicillin-resistant Staphylococcus aureus (MuH MRSA). Diagn. Microbiol. Infect. Dis. 82, 278–283 (2015). This paper shows multiple efflux gene carriage in Staphylococcus aureus clinical isolates, where most of the isolates harbour two or more efflux pump gene determinants.

    Article  CAS  PubMed  Google Scholar 

  142. Hijazi, K. et al. Susceptibility to chlorhexidine amongst multidrug-resistant clinical isolates of Staphylococcus epidermidis from bloodstream infections. Int. J. Antimicrob. Agents 48, 86–90 (2016).

    Article  CAS  PubMed  Google Scholar 

  143. Conceição, T., Coelho, C., de Lencastre, H. & Aires-de-Sousa, M. High prevalence of biocide resistance determinants in Staphylococcus aureus isolates from three African countries. Antimicrob. Agents Chemother. 60, 678–681 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  144. Wand, M. E. et al. Characterization of pre-antibiotic era Klebsiella pneumoniae isolates with respect to antibiotic/disinfectant susceptibility and virulence in Galleria mellonella. Antimicrob. Agents Chemother. 59, 3966–3972 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Lin, F. et al. Molecular characterization of reduced susceptibility to biocides in clinical isolates of Acinetobacter baumannii. Front. Microbiol. 8, 1836 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  146. Elkhatib, W. F., KhaIiI, M. A. F. & Ashour, H. M. Integrons and antiseptic resistance genes mediate resistance of Acinetobacter baumannii and Pseudomonas aeruginosa isolates from intensive care unit patients with wound infections. Curr. Mol. Med. 19, 286–293 (2019).

    Article  CAS  PubMed  Google Scholar 

  147. Goodarzi, R., Yousefimashouf, R., Taheri, M., Nouri, F. & Asghari, B. Susceptibility to biocides and the prevalence of biocides resistance genes in clinical multidrug-resistant Pseudomonas aeruginosa isolates from Hamadan, Iran. Mol. Biol. Rep. 48, 5275–5281 (2021).

    Article  CAS  PubMed  Google Scholar 

  148. Namaki, M. et al. Prevalence of resistance genes to biocides in antibiotic-resistant Pseudomonas aeruginosa clinical isolates. Mol. Biol. Rep. 49, 2149–2155 (2022).

    Article  CAS  PubMed  Google Scholar 

  149. Boutarfi, Z. et al. Biocide tolerance and antibiotic resistance of Enterobacter spp. isolated from an Algerian hospital environment. J. Glob. Antimicrob. Res. 18, 291–297 (2019).

    Article  Google Scholar 

  150. Medardus, J. J. et al. In-feed use of heavy metal micronutrients in U.S. swine production systems and its role in persistence of multidrug-resistant Salmonellae. Appl. Environ. Microbiol. 80, 2317–2325 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  151. Correa, J. E., De Paulis, A., Predari, S., Sordelli, D. O. & Jeric, P. E. First report of qacG, qacH and qacJ genes in Staphylococcus haemolyticus human clinical isolates. J. Antimicrob. Chemother. 62, 956–960 (2008).

    Article  CAS  PubMed  Google Scholar 

  152. Jiang, X. et al. Examination of quaternary ammonium compound resistance in Proteus mirabilis isolated from cooked meat products in China. Front. Microbiol. 8, 2417 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  153. Jiang, X. et al. Characterization and horizontal transfer of qacH-associated class 1 integrons in Escherichia coli isolated from retail meats. Int. J. Food Microbiol. 258, 12–17 (2017).

    Article  CAS  PubMed  Google Scholar 

  154. Wales, A. D. & Davies, R. H. Co-selection of resistance to antibiotics, biocides and heavy metals, and its relevance to foodborne pathogens. Antibiotics 4, 567–604 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  155. Pal, C. et al. Metal resistance and its association with antibiotic resistance. Adv. Microb. Physiol. 70, 261–313 (2017).

    Article  CAS  PubMed  Google Scholar 

  156. Sidhu, M. S., Heir, E., Leegaard, T., Wiger, K. & Holck, A. Frequency of disinfectant resistance genes and genetic linkage with beta-lactamase transposon Tn552 among clinical staphylococci. Antimicrob. Agents Chemother. 46, 2797–2803 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Harrison, K. R., Kappell, A. D. & McNamara, P. J. Benzalkonium chloride alters phenotypic and genotypic antibiotic resistance profiles in a source water used for drinking water treatment. Environ. Poll. 257, 113472 (2020).

    Article  CAS  Google Scholar 

  158. Siani, H. & Maillard, J.-Y. Best practice in healthcare environment decontamination. Eur. J. Infect. Control. Infect. Dis. 34, 1–11 (2015).

    CAS  Google Scholar 

  159. Van Asselt, A.J. & te Giffel, M. C. in Handbook of Hygiene Control in the Food Industry (eds Lelieveld, H. L. M., Mostert, M. A. & Holah, J.) 69–92 (Woodhead Publishing, 2005).

  160. Maillard, J.-Y. et al. Reducing antibiotic prescribing and addressing the global problem of antibiotic resistance by targeted hygiene in the home and everyday life settings: a position paper. Am. J. Infect. Control. 48, 1090–1099 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  161. Wellcome Trust. The Global Response to AMR. Momentum, Success, and Critical Gaps. Wellcome Trust https://cms.wellcome.org/sites/default/files/2020-11/wellcome-global-response-amr-report.pdf (2020).

  162. O’Neil, J. Tackling Drug-Resistant Infections Globally; Final Report and Recommendations. Wellcome Trust and HM Government https://amr-review.org/sites/default/files/160518_Final%20paper_with%20cover.pdf (2016).

  163. Zhang, M., Chen, L., Ye, C. & Yu, X. Co-selection of antibiotic resistance via copper sock loading on bacteria from drinking water bio-filter. Eviron. Poll. 233, 132–141 (2018).

    Article  CAS  Google Scholar 

  164. Fernando, D. M., Xu, W., Loewen, P. C., Zhanel, G. G. & Kumar, A. Triclosan can select for an AdeIJK-overexpressing mutant of Acinetobacter baumannii ATCC 17978 that displays reduced susceptibility to multiple antibiotics. Antimicrob. Agents Chemother. 58, 6424–6431 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  165. Mc Cay, P. H., Ocampo-Sosa, A. O. & Fleming, G. T. A. Effect of subinhibitory concentrations of benzalkonium chloride on the competitiveness of Pseudomonas aeruginosa grown in continuous culture. Microbiology 156, 30–38 (2010).

    Article  Google Scholar 

  166. Mavri, A. & Smole Možina, S. Development of antimicrobial resistance in Campylobacter jejuni and Campylobacter coli adapted to biocides. Int. J. Food Microbiol. 160, 304–312 (2013).

    Article  CAS  PubMed  Google Scholar 

  167. Tong, C. et al. Chlorine disinfectants promote microbial resistance in Pseudomonas sp. Environ. Res. 199, 111296 (2021).

    Article  CAS  PubMed  Google Scholar 

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    Jean-Yves Maillard & Michael Pascoe

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Maillard, JY., Pascoe, M. Disinfectants and antiseptics: mechanisms of action and resistance. Nat Rev Microbiol 22, 4–17 (2024). https://doi.org/10.1038/s41579-023-00958-3

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