Vet Med - Czech, 2012, 57(6):275-281 | DOI: 10.17221/6013-VETMED

Genetic basis of resistance to quaternary ammonium compounds - the qac genes and their role: a review

Z. Jaglic, D. Cervinkova
Veterinary Research Institute, Brno, Czech Republic

Although the qac genes are named after one of their main substrates (i.e., quaternary ammonium compounds), these genes also code for resistance to a broad spectrum of other cationic compounds such as intercalating dyes, diamidines and biguanides. The various Qac proteins are involved in relatively low specific efflux-based multidrug pumps and belong to a family of small multidrug resistance proteins. Even though the practical significance of qac-mediated resistance lies mainly in resistance to antiseptics, contradictory findings on this issue are still reported. Therefore, the aim of this review is to summarise the current knowledge on qac-mediated resistance with special emphasis on resistance to antiseptics and its relevance for practice.

Keywords: antimicrobial; disinfectant; biocide; benzalkonium; chlorhexidine; cation; susceptibility

Published: June 30, 2012  Show citation

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Jaglic Z, Cervinkova D. Genetic basis of resistance to quaternary ammonium compounds - the qac genes and their role: a review. Vet Med - Czech. 2012;57(6):275-281. doi: 10.17221/6013-VETMED.
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    References

    1. Alam MM, Kobayashi N, Uehara N, Watanabe N (2003): Analysis on distribution and genomic diversity of highlevel antiseptic resistance genes qacA and qacB in human clinical isolates of Staphylococcus aureus. Microbial Drug Resistance-Mechanisms Epidemiology and Disease 9, 109-121. Go to original source... Go to PubMed...
    2. Archer GL, Johnston JL (1983): Self-transmissible plasmids in staphylococci that encode resistance to aminoglycosides. Antimicrobial Agents and Chemotherapy 24, 70-77. Go to original source... Go to PubMed...
    3. Bass L, Liebert CA, Lee MD, Summers AO, White DG, Thayer SG, Maurer JJ (1999): Incidence and characterization of integrons, genetic elements mediating multiple-drug resistance, in avian Escherichia coli. Antimicrobial Agents and Chemotherapy 43, 2925-2929. Go to original source... Go to PubMed...
    4. Bay DC, Turner RJ (2009): Diversity and evolution of the small multidrug resistance protein family. BMC Evolutionary Biology 9, 140. Go to original source... Go to PubMed...
    5. Bayer AS, Kupferwasser LI, Brown MH, Skurray RA, Grkovic S, Jones T, Mukhopadhay K, Yeaman MR (2006): Low-level resistance of Staphylococcus aureus to thrombin-induced platelet microbicidal protein 1 in vitro associated with qacA gene carriage is independent of multidrug efflux pump activity. Antimicrobial Agents and Chemotherapy 50, 2448-2454. Go to original source... Go to PubMed...
    6. Behr H, Reverdy ME, Mabilat C, Freney J, Fleurette J (1994): Relationship between the MIC levels of 5 antiseptics and presence of the qacA gene in Staphylococcus aureus (in French). Pathologie et Biologie 42, 438-444. Go to PubMed...
    7. Bischoff M, Bauer J, Preikschat P, Schwaiger K, Molle G, Holzel C (2012): First detection of the antiseptic resistance gene qacA/B in Enterococcus faecalis. Microbial Drug Resistance 18, 7-12. Go to original source... Go to PubMed...
    8. Bjorland J, Steinum T, Sunde M, Waage S, Heir E (2003): Novel plasmid-borne gene qacJ mediates resistance to quaternary ammonium compounds in equine Staphylococcus aureus, Staphylococcus simulans, and Staphylococcus intermedius. Antimicrobial Agents and Chemotherapy 47, 3046-3052. Go to original source... Go to PubMed...
    9. Bjorland J, Steinum T, Kvitle B, Waage S, Sunde M, Heir E (2005): Widespread distribution of disinfectant resistance genes among staphylococci of bovine and caprine origin in Norway. Journal of Clinical Microbiology 43, 4363-4368. Go to original source... Go to PubMed...
    10. Borgianni L, Prandi S, Salden L, Santella G, Hanson ND, Rossolini GM, Docquier JD (2011): Genetic context and biochemical characterization of the IMP-18 metallo-beta-lactamase identified in a Pseudomonas aeruginosa isolate from the United States. Antimicrobial Agents and Chemotherapy 55, 140-145. Go to original source... Go to PubMed...
    11. Braga TM, Marujo PE, Pomba C, Lopes MFS (2011): Involvement, and dissemination, of the enterococcal small multidrug resistance transporter QacZ in resistance to quaternary ammonium compounds. Journal of Antimicrobial Chemotherapy 66, 283-286. Go to original source... Go to PubMed...
    12. Brown MH, Skurray RA (2001): Staphylococcal multidrug efflux protein QacA. Journal of Molecular Microbiology and Biotechnology 3, 163-170. Go to PubMed...
    13. Chang YC, Shih DYC, Wang JY, Yang SS (2007): Molecular characterization of class 1 integrons and antimicrobial resistance in Aeromonas strains from foodborne outbreak-suspect samples and environmental sources in Taiwan. Diagnostic Microbiology and Infectious Disease 59, 191-197. Go to original source... Go to PubMed...
    14. Colinon C, Jocktane D, Brothier E, Rossolini GM, Cournoyer B, Nazaret S (2010): Genetic analyses of Pseudomonas aeruginosa isolated from healthy captive snakes: evidence of high inter- and intrasite dissemination and occurrence of antibiotic resistance genes. Environmental Microbiology 12, 716-729. Go to original source... Go to PubMed...
    15. DeMarco CE, Cushing LA, Frempong-Manso E, Seo SM, Jaravaza TAA, Kaatz GW (2007): Efflux-related resistance to norfloxacin, dyes, and biocides in bloodstream isolates of Staphylococcus aureus. Antimicrobial Agents and Chemotherapy 51, 3235-3239. Go to original source... Go to PubMed...
    16. Ericson C (1969): Resistance to acriflavine and cadmium and changed phage reactions - markers of a new staphylococcal penicillinase plasmid. Acta Pathologica et Microbiologica Scandinavica 76, 333.
    17. Espedido BA, Partridge SR, Iredell JR (2008): bla(IMP-4) in different genetic contexts in Enterobacteriaceae isolates from Australia. Antimicrobial Agents and Chemotherapy 52, 2984-2987. Go to original source... Go to PubMed...
    18. Fuentes DE, Navarro CA, Tantalean JC, Araya MA, Saavedra CP, Perez JM, Calderon IL, Youderian PA, Mora GC, Vasquez CC (2005): The product of the qacC gene of Staphylococcus epidermidis CH mediates resistance to beta-lactam antibiotics in Gram-positive and Gram-negative bacteria. Research in Microbiology 156, 472-477. Go to original source... Go to PubMed...
    19. Galluzzi L, Virtanen P, Karp M (2003): A real-time analysis of QacR-regulated multidrug resistance in Staphylococcus aureus. Biochemical and Biophysical Research Communications 301, 24-30. Go to original source... Go to PubMed...
    20. Gillespie MT, May JW, Skurray RA (1986): Plasmid-encoded resistance to acriflavine and quaternary ammonium compounds in methicillin-resistant Staphylococcus aureus. Fems Microbiology Letters 34, 47-51. Go to original source...
    21. Grkovic S, Hardie KM, Brown MH, Skurray RA (2003): Interactions of the QacR multidrug-binding protein with structurally diverse ligands: implications for the evolution of the binding pocket. Biochemistry 42, 15226-15236. Go to original source... Go to PubMed...
    22. Hassan KA, Galea M, Wu JQ, Mitchell BA, Skurray RA, Brown MH (2006): Functional effects of intramembranous proline substitutions in the staphylococcal multidrug transporter QacA. Fems Microbiology Letters 263, 76-85. Go to original source... Go to PubMed...
    23. Hegstad K, Langsrud S, Lunestad BT, Scheie AA, Sunde M, Yazdankhah SP (2010): Does the wide use of quaternary ammonium compounds enhance the selection and spread of antimicrobial resistance and thus threaten our health? Microbial Drug Resistance 16, 91-104. Go to original source... Go to PubMed...
    24. Heir E, Sundheim G, Holck AL (1995): Resistance to quaternary ammonium compounds in Staphylococcus spp. isolated from the food industry and nucleotide sequence of the resistance plasmid pST827. Journal of Applied Bacteriology, 79, 149-156. Go to original source... Go to PubMed...
    25. Heir E, Sundheim G, Holck AL (1998): The Staphylococcus qacH gene product: a new member of the SMR family encoding multidrug resistance. FEMS Microbiology Letters 163, 49-56. Go to original source... Go to PubMed...
    26. Heir E, Sundheim G, Holck AL (1999): The qacG gene on plasmid pST94 confers resistance to quaternary ammonium compounds in staphylococci isolated from the food industry. Journal of Applied Microbiology 86, 378-388. Go to original source... Go to PubMed...
    27. Jaglic Z, Cervinkova D, Vlkova H, Michu E, Kunova G, Babak V (2012): Bacterial biofilms resist oxidising agents due to the presence of organic matter. Czech Journal of Food Sciences 30, 178-187. Go to original source...
    28. Jeong JH, Shin KS, Lee JW, Park EJ, Son SY (2009): Analysis of a novel class 1 integron containing metallo-betalactamase gene VIM-2 in Pseudomonas aeruginosa. Journal of Microbiology 47, 753-759. Go to original source... Go to PubMed...
    29. Johnston LH, Dyke KGH (1969): Ethidium bromide resistance, a new marker on the staphylococcal penicillinase plasmid. Journal of Bacteriology 100, 1413-1414. Go to original source... Go to PubMed...
    30. Jones IG, Midgley M (1985): Expression of a plasmid borne ethidium resistance determinant from Staphylococcus in Escherichia coli - evidence for an efflux system. FEMS Microbiology Letters 28, 355-358. Go to original source...
    31. Kawai M, Yamada S, Ishidoshiro A, Oyamada Y, Ito H, Yamagishi J (2009): Cell-wall thickness: possible mechanism of acriflavine resistance in meticillin-resistant Staphylococcus aureus. Journal of Medical Microbiology 58, 331-336. Go to original source... Go to PubMed...
    32. Kazama H, Hamashima H, Sasatsu M, Arai T (1998): Distribution of the antiseptic-resistance gene qacE delta 1 in Gram-positive bacteria. FEMS Microbiology Letters 165, 295-299. Go to original source... Go to PubMed...
    33. Kucken D, Feucht HH, Kaulfers PM (2000): Association of qacE and qacE delta 1 with multiple resistance to antibiotics and antiseptics in clinical isolates of Gram-negative bacteria. FEMS Microbiology Letters 183, 95-98. Go to original source... Go to PubMed...
    34. Langsrud S, Sundheim G, Holck AL (2004): Cross-resistance to antibiotics of Escherichia coli adapted to benzalkonium chloride or exposed to stress-inducers. Journal of Applied Microbiology 96, 201-208. Go to original source... Go to PubMed...
    35. Leelaporn A, Paulsen IT, Tennent JM, Littlejohn TG, Skurray RA (1994): Multidrug resistance to antiseptics and disinfectants in coagulase-negative staphylococci. Journal of Medical Microbiology 40, 214-220. Go to original source... Go to PubMed...
    36. Littlejohn TG, DiBerardino D, Messerotti LJ, Spiers SJ, Skurray RA (1991): Structure and evolution of a family of genes encoding antiseptic and disinfectant resistance in Staphylococcus aureus. Gene 101, 59-66. Go to original source... Go to PubMed...
    37. Littlejohn TG, Paulsen IT, Gillespie MT, Tennent JM, Midgley M, Jones IG, Purewal AS, Skurray RA (1992): Substrate specificity and energetics of antiseptic and disinfectant resistance in Staphylococcus aureus. FEMS Microbiology Letters 95, 259-266. Go to original source...
    38. Liu QZ, Liu MN, Wu Q, Li C, Zhou TL, Ni YX (2009): Sensitivities to biocides and distribution of biocide resistance genes in quaternary ammonium compound tolerant Staphylococcus aureus isolated in a teaching hospital. Scandinavian Journal of Infectious Diseases 41, 403-409. Go to original source... Go to PubMed...
    39. Longtin J, Seah C, Siebert K, McGeer A, Simor A, Longtin Y, Low DE, Melano RG (2011): Distribution of antiseptic resistance genes qacA, qacB, and smr in methicillin-resistant Staphylococcus aureus isolated in Toronto, Canada, from 2005 to 2009. Antimicrobial Agents and Chemotherapy 55, 2999-3001. Go to original source... Go to PubMed...
    40. Lyon BR, Skurray R (1987): Antimicrobial resistance of Staphylococcus aureus - genetic-basis. Microbiological Reviews 51, 88-134. Go to original source... Go to PubMed...
    41. Lyon BR, May JW, Skurray RA (1984): Tn4001 - a gentamicin and kanamycin resistance transposon in Staphylococcus aureus. Molecular and General Genetics 193, 554-556. Go to original source... Go to PubMed...
    42. Mak JK, Kim MJ, Pham J, Tapsall J, White PA (2009): Antibiotic resistance determinants in nosocomial strains of multidrug-resistant Acinetobacter baumannii. Journal of Antimicrobial Chemotherapy 63, 47-54. Go to original source... Go to PubMed...
    43. Mayer S, Boos M, Beyer A, Fluit AC, Schmitz FJ (2001): Distribution of the antiseptic resistance genes qacA, qacB and qacC in 497 methicillin-resistant and -susceptible European isolates of Staphylococcus aureus. Journal of Antimicrobial Chemotherapy, 47, 896-897. Go to original source... Go to PubMed...
    44. McDonnell G, Russell AD (1999): Antiseptics and disinfectants: Activity, action, and resistance. Clinical Microbiology Reviews 12, 147-179. Go to original source... Go to PubMed...
    45. McDonnell RW, Sweeney HM, Cohen S (1983): Conjugational transfer of gentamicin resistance plasmids intraspecifically and interspecifically in Staphylococcus aureus and Staphylococcus epidermidis. Antimicrobial Agents and Chemotherapy 23, 151-160. Go to original source... Go to PubMed...
    46. McGann P, Kwak YI, Summers A, Cummings JF, Waterman PE, Lesho EP (2011): Detection of qacA/B in clinical isolates of methicillin-resistant Staphylococcus aureus from a regional healthcare network in the eastern United States. Infection Control and Hospital Epidemiology 32, 1116-1119. Go to original source... Go to PubMed...
    47. Mitchell BA, Brown MH, Skurray RA (1998): QacA multidrug efflux pump from Staphylococcus aureus: comparative analysis of resistance to diamidines, biguanidines, and guanylhydrazones. Antimicrobial Agents and Chemotherapy 42, 475-477. Go to original source... Go to PubMed...
    48. Noguchi N, Suwa J, Narui K, Sasatsu M, Ito T, Hiramatsu K, Song JH (2005): Susceptibilities to antiseptic agents and distribution of antiseptic-resistance genes qacA/B and smr of methicillin-resistant Staphylococcus aureus isolated in Asia during 1998 and 1999. Journal of Medical Microbiology 54, 557-565. Go to original source... Go to PubMed...
    49. Paulsen IT, Brown MH, Dunstan SJ, Skurray RA (1995): Molecular characterization of the staphylococcal multidrug-resistance export protein QacC. Journal of Bacteriology 177, 2827-2833. Go to original source... Go to PubMed...
    50. Ploy MC, Courvalin P, Lambert T (1998): Characterization of In40 of Enterobacter aerogenes BM2688, a class 1 integron with two new gene cassettes, cmlA2 and qacF. Antimicrobial Agents and Chemotherapy 42, 2557-2563. Go to original source... Go to PubMed...
    51. Poirel L, Le Thomas I, Naas T, Karim A, Nordmann P (2000): Biochemical sequence analyses of GES-1, a novel class A extended-spectrum beta-lactamase, and the class 1 integron In52 from Klebsiella pneumoniae. Antimicrobial Agents and Chemotherapy 44, 622-632. Go to original source... Go to PubMed...
    52. Poole TL, Callaway TR, Bischoff KM, Warnes CE, Nisbet DJ (2006): Macrolide inactivation gene cluster mphAmrx-mphR adjacent to a class 1 integron in Aeromonas hydrophila isolated from a diarrhoeic pig in Oklahoma. Journal of Antimicrobial Chemotherapy 57, 31-38. Go to original source... Go to PubMed...
    53. Riano I, Moreno MA, Teshager T, Saenz Y, Dominguez L, Torres C (2006): Detection and characterization of extended-spectrum beta-lactamases in Salmonella enterica strains of healthy food animals in Spain. Journal of Antimicrobial Chemotherapy 58, 844-847. Go to original source... Go to PubMed...
    54. Romao C, Miranda CA, Silva J, Clementino MM, de Filippis I, Asensi M (2011): Presence of qacE delta 1 gene and susceptibility to a hospital biocide in clinical isolates of Pseudomonas aeruginosa resistant to antibiotics. Current Microbiology 63, 16-21. Go to original source... Go to PubMed...
    55. Rosser SJ, Young HK (1999): Identification and characterization of class 1 integrons in bacteria from an aquatic environment. Journal of Antimicrobial Chemotherapy 44, 11-18. Go to original source... Go to PubMed...
    56. Rouch DA, Cram DS, Diberardino D, Littlejohn TG, Skurray RA (1990): Efflux-mediated antiseptic resistance gene qacA from Staphylococcus aureus - common ancestry with tetracycline-transport and sugar-transport proteins. Molecular Microbiology 4, 2051-2062. Go to original source... Go to PubMed...
    57. Russell AD (2000): Do biocides select for antibiotic resistance? Journal of Pharmacy and Pharmacology 52, 227-233. Go to original source... Go to PubMed...
    58. Sheng WH, Wang JT, Lauderdale TL, Weng CM, Chen DL, Chang SC (2009): Epidemiology and susceptibilities of methicillin-resistant Staphylococcus aureus in Taiwan: emphasis on chlorhexidine susceptibility. Diagnostic Microbiology and Infectious Disease 63, 309-313. Go to original source... Go to PubMed...
    59. Smith K, Gemmell CG, Hunter IS (2008): The association between biocide tolerance and the presence or absence of qac genes among hospital-acquired and communityacquired MRSA isolates. Journal of Antimicrobial Chemotherapy 61, 78-84. Go to original source... Go to PubMed...
    60. Soufi L, Abbassi MS, Saenz Y, Vinue L, Somalo S, Zarazaga M, Abbas A, Dbaya R, Khanfir L, Ben Hassen A, Hammami S, Torres C (2009): Prevalence and diversity of integrons and associated resistance genes in Escherichia coli isolates from poultry meat in Tunisia. Foodborne Pathogens and Disease 6, 1067-1073. Go to original source... Go to PubMed...
    61. Sundheim G, Langsrud S, Heir E, Holck AL (1998): Bacterial resistance to disinfectants containing quaternary ammonium compounds. International Biodeterioration and Biodegradation 41, 235-239. Go to original source...
    62. Szczepanowski R, Krahn I, Linke B, Goesmann A, Puhler A, Schluter A (2004): Antibiotic multiresistance plasmid pRSB101 isolated from a wastewater treatment plant is related to plasmids residing in phytopathogenic bacteria and carries eight different resistance determinants including a multidrug transport system. Microbiology-SGM 150, 3613-3630. Go to original source... Go to PubMed...
    63. Tennent JM, Lyon BR, Midgley M, Jones IG, Purewal AS, Skurray RA (1989): Physical and biochemical characterization of the qacA gene encoding antiseptic and disinfectant resistance in Staphylococcus aureus. Journal of General Microbiology 135, 1-10. Go to original source... Go to PubMed...
    64. Theis T, Skurray RA, Brown MH (2007): Identification of suitable internal controls to study expression of a Staphylococcus aureus multidrug resistance system by quantitative real-time PCR. Journal of Microbiological Methods 70, 355-362. Go to original source... Go to PubMed...
    65. Vali L, Davies SE, Lai LLG, Dave J, Amyes SGB (2008): Frequency of biocide resistance genes, antibiotic resistance and the effect of chlorhexidine exposure on clinical methicillin-resistant Staphylococcus aureus isolates. Journal of Antimicrobial Chemotherapy 61, 524-532. Go to original source... Go to PubMed...
    66. Wang C, Zhan Q, Mi Z, Huang Z, Chen G (2008a): Distribution of the antiseptic-resistance gene qacE delta 1 in 283 clinical isolates of Gram-negative bacteria in China. Journal of Hospital Infection 69, 394-396. Go to original source... Go to PubMed...
    67. Wang JT, Sheng WH, Wang JL, Chen D, Chen ML, Chen YC, Chang SC (2008b): Longitudinal analysis of chlorhexidine susceptibilities of nosocomial methicillinresistant Staphylococcus aureus isolates at a teaching hospital in Taiwan. Journal of Antimicrobial Chemotherapy 62, 514-517. Go to original source... Go to PubMed...
    68. Wannaprasat W, Padungtod P, Chuanchuen R (2011): Class 1 integrons and virulence genes in Salmonella enterica isolates from pork and humans. International Journal of Antimicrobial Agents 37, 457-461. Go to original source... Go to PubMed...
    69. Weigel LM, Clewell DB, Gill SR, Clark NC, McDougal LK, Flannagan SE, Kolonay JF, Shetty J, Killgore GE, Tenover FC (2003): Genetic analysis of a high-level vancomycin-resistant isolate of Staphylococcus aureus. Science 302, 1569-1571. Go to original source... Go to PubMed...
    70. Ye HF, Zhang M, O'Donoghue M, Boost M (2012): Are qacG, qacH and qacJ genes transferring from food isolates to carriage isolates of staphylococci? Journal of Hospital Infection 80, 95-96. Go to original source... Go to PubMed...
    71. Zhao WH, Chen GL, Ito R, Kimura S, Hu ZQ (2012): Identification of a plasmid-borne bla(IMP-11) gene in clinical isolates of Escherichia coli and Klebsiella pneumoniae. Journal of Medical Microbiology 61, 246-251. Go to original source... Go to PubMed...
    72. Zmantar T, Kouidhi B, Hentati H, Bakhrouf A (2012): Detection of disinfectant and antibiotic resistance genes in Staphylococcus aureus isolated from the oral cavity of Tunisian children. Annals of Microbiology 62, 123-128. Go to original source...

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