Skip to main content
SpringerLink
Log in

The impact and mechanism of quaternary ammonium compounds on the transmission of antibiotic resistance genes

  • Research Article
  • Published:
Environmental Science and Pollution Research Aims and scope Submit manuscript

Abstract

The emergence of antibiotic resistance genes (ARGs) in microbes can be largely attributed to the abuse and misuse of antibiotics and biocides. Quaternary ammonium compounds (QACs) have been used worldwide as common disinfectants and detergents; however, their potential impact on the spread and diffusion of ARGs is still unknown. In this study, we detected the QAC resistance gene (qacEΔ1), the 1 integron gene (intI1), and 12 ARGs (sul1, sul2, cfr, cml, fexA, tetA, tetG, tetQ, tetX, ermB, blaTEM, and dfrA1) in 48 water samples from three watersheds by quantitative PCR (qPCR). We investigated the evolution of bacterial antibiotic resistance under QAC and antibiotic environmental pressures by long-term continuous culture. In addition, five QACs were selected to investigate the effect of QAC on the efficiency of conjugation transfer. The changes in bacterial cell membrane and production of reactive oxygen species (ROS) were detected by flow cytometry, revealing the mechanism by which QAC affects the spread of antibiotic resistance. Our results showed that the QAC resistance gene was ubiquitous in watersheds and it had significant correlation with intI1 and seven ARGs (r = 0.999, p < 0.01). QACs could increase the resistance of bacteria to multiple antibiotics. Furthermore, all five QACs promoted the conjugation transfer of the RP4 plasmid; the optimal concentration of QACs was about 10−1–10−2 mg/L and their transfer efficiencies were between 1.33 × 10−6 and 8.87 × 10−5. QACs enhanced membrane permeability of bacterial cells and stimulated bacteria to produce ROS, which potentially promoted the transfer of plasmids between bacteria. In conclusion, this study demonstrated that QACs may facilitate the evolution and gene transfer of antibiotic resistance gene among microbiome.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Alekshun MN, Levy SB (2007) Molecular mechanisms of antibacterial multidrug resistance. Cell 128:1037–1050

    Article  CAS  Google Scholar 

  • Bakeraustin C, Wright MS, Stepanauskas R, Mcarthur JV (2006) Co-selection of antibiotic and metal resistance. Trends Microbiol 14:176–182

    Article  CAS  Google Scholar 

  • Bouzada ML, Silva VL, Moreira FA, Silva GA, Diniz CG (2010) Antimicrobial resistance and disinfectants susceptibility of persistent bacteria in a tertiary care hospital. J Microbiol Antimicrob 2:105–112

    Google Scholar 

  • Brazas MD, Hancock RE (2005) Ciprofloxacin induction of a susceptibility determinant in Pseudomonas aeruginosa. Antimicrob Agents Chemother 49:3222–3227

    Article  CAS  Google Scholar 

  • Chapman JS (2003) Disinfectant resistance mechanisms, cross-resistance, and co-resistance. Int Biodeterior Biodegrad 51:271–276

    Article  CAS  Google Scholar 

  • Chen I, Christie PJ, Dubnau D (2005) The ins and outs of DNA transfer in bacteria. Science 310:1456–1460

    Article  CAS  Google Scholar 

  • Cui E, Wu Y, Zuo Y, Chen H (2016) Effect of different biochars on antibiotic resistance genes and bacterial community during chicken manure composting. Bioresour Technol 203:11–17

    Article  CAS  Google Scholar 

  • García MT, Campos E, Sanchez-Leal J, Ribosa I (1999) Effect of the alkyl chain length on the anaerobic biodegradability and toxicity of quaternary ammonium based surfactants. Chemosphere 38:3473–3483

    Article  Google Scholar 

  • Gaze WH, Zhang L, Abdouslam NA, Hawkey PM, Calvobado L, Royle J, Brown H, Davis S, Kay P, Boxall ABA (2011) Impacts of anthropogenic activity on the ecology of class 1 integrons and integron-associated genes in the environment. ISME J 5:1253–1261

    Article  CAS  Google Scholar 

  • Gilbert P, Moore LE (2005) Cationic antiseptics: diversity of action under a common epithet. J Appl Microbiol 99:703–715

    Article  CAS  Google Scholar 

  • Gillings MR, Duan X, Hardwick SA, Holley MP, Stokes HW (2009a) Gene cassettes encoding resistance to quaternary ammonium compounds: a role in the origin of clinical class 1 integrons? ISME J. 3:209–215

    Article  CAS  Google Scholar 

  • Gillings MR, Holley MP, Stokes HW (2009b) Evidence for dynamic exchange of qac gene cassettes between class 1 integrons and other integrons in freshwater biofilms. FEMS Microbiol Lett 296:282–288

    Article  CAS  Google Scholar 

  • Gillings MR, Gaze WH, Pruden A, Smalla K, Tiedje JM, Zhu YG (2015) Using the class 1 integron-integrase gene as a proxy for anthropogenic pollution. ISME J. 9:1269–1279

    Article  CAS  Google Scholar 

  • Heerklotz H (2008) Interactions of surfactants with lipid membranes. Q Rev Biophys 41:205–264

    Article  CAS  Google Scholar 

  • 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? Microb Drug Resist 16:91–104

    Article  CAS  Google Scholar 

  • Holmberg K (2002) Handbook of applied surface and colloid chemistry. Aust J Chem 55:383–402

    Google Scholar 

  • Jansen AC, Boucher CE, Coetsee E, Kock JLF, Wyk PWJV, Swart HC, Bragg RR (2013) The influence of didecyldimethylammonium chloride on the morphology and elemental composition of Staphylococcus aureus as determined by NanoSAM. Sci Res Essays 8:152–160

    CAS  Google Scholar 

  • Jiao YN, Chen H, Gao RX, Zhu YG, Rensing C (2017) Organic compounds stimulate horizontal transfer of antibiotic resistance genes in mixed wastewater treatment systems. Chemosphere 184:53–61

    Article  CAS  Google Scholar 

  • Jutkina J, Marathe NP, Flach CF, Larsson DGJ (2018) Antibiotics and common antibacterial biocides stimulate horizontal transfer of resistance at low concentrations. Sci Total Environ 616-617:172–178

    Article  CAS  Google Scholar 

  • Kholodii GY, Mindlin SZ, Bass IA, Yurieva OV, Minakhina SV, Nikiforov VG (1995) Four genes, two ends, and a res region are involved in transposition of Tn5053: a paradigm for a novel family of transposons carrying either a mer operon or an integron. Mol Microbiol 17:1189–1200

    Article  CAS  Google Scholar 

  • Levin-Reisman I, Ronin I, Gefen O, Braniss I, Shoresh N, Balaban NQ (2017) Antibiotic tolerance facilitates the evolution of resistance. Science 355(6327):826–830

    Article  CAS  Google Scholar 

  • Li X, Brownawell BJ (2010) Quaternary ammonium compounds in urban estuarine sediment environments—a class of contaminants in need of increased attention? Environ Sci Technol 44:7561–7568

    Article  CAS  Google Scholar 

  • Li D, Zeng S, He M, Gu AZ (2016) Water disinfection byproducts induce antibiotic resistance-role of environmental pollutants in resistance phenomena. Environ Sci Technol 50(6):3193–3201

    Article  CAS  Google Scholar 

  • Liu WJ, Fu L, Huang M, Zhang JP, Wu Y, Zhou YS, Zeng J, Wang GX (2017) Frequency of antiseptic resistance genes and reduced susceptibility to biocides in carbapenem-resistant Acinetobacter baumannii. J Med Microbiol 66

  • Lopatkin AJ, Huang S, Smith RP, Srimani JK, Sysoeva TA, Bewick S, Karig DK, You L (2016) Antibiotics as a selective driver for conjugation dynamics. Nat Microbiol 1:16044

    Article  CAS  Google Scholar 

  • Loughlin MF, Jones MV, Lambert PA (2002) Pseudomonas aeruginosa cells adapted to benzalkonium chloride show resistance to other membrane-active agents but not to clinically relevant antibiotics. J Antimicrob Chemother 49:631–639

    Article  CAS  Google Scholar 

  • Luo Y, Wang Q, Lu Q, Mu Q, Mao D (2014) An ionic liquid facilitates the proliferation of antibiotic resistance genes mediated by class I integrons. Environ Sci Technol Lett 1:266–270

    Article  CAS  Google Scholar 

  • Maillard JY (2002) Bacterial target sites for biocide action. J Appl Microbiol 92:16S–27S

    Article  Google Scholar 

  • Marathe NP, Pal C, Gaikwad SS, Jonsson V, Kristiansson E, Dgj L (2017) Untreated urban waste contaminates Indian river sediments with resistance genes to last resort antibiotics. Water Res 124:388–397

    Article  CAS  Google Scholar 

  • Mc Cay PH, Ocampo-Sosa AA, Fleming GT (2010) Effect of subinhibitory concentrations of benzalkonium chloride on the competitiveness of Pseudomonas aeruginosa grown in continuous culture. Microbiology 156:30–38

    Article  CAS  Google Scholar 

  • Mcdonnell G, Russell AD (1999) Antiseptics and disinfectants: activity, action, and resistance. Clin Microbiol Rev 12:147–179

    Article  CAS  Google Scholar 

  • Mcmanus PS, Stockwell VO, Sundin GW, Jones AL (2002) Antibiotic use in plant agriculture. Annu Rev Phytopathol 40:443–465

    Article  CAS  Google Scholar 

  • Moriguchi K, Yamamoto S, Ohmine Y, Suzuki K (2016) A fast and practical yeast transformation method mediated by Escherichia coli based on a trans-kingdom conjugal transfer system: just mix two cultures and wait one hour. PLoS One 11:e0148989

    Article  CAS  Google Scholar 

  • Nagai K, Murata T, Ohta S, Zenda H, Ohnishi M, Hayashi T (2003) Two different mechanisms are involved in the extremely high-level benzalkonium chloride resistance of a Pseudomonas fluorescens strain. Microbiol Immunol 47:709–715

    Article  CAS  Google Scholar 

  • Pal C, Bengtssonpalme J, Kristiansson E, Larsson DG (2015) Co-occurrence of resistance genes to antibiotics, biocides and metals reveals novel insights into their co-selection potential. BMC Genomics 16:1–14

    Article  CAS  Google Scholar 

  • Patrauchan MA, Oriel PJ (2003) Degradation of benzyldimethylalkylammonium chloride by Aeromonas hydrophila sp. K. J Appl Microbiol 94:266–272

    Article  CAS  Google Scholar 

  • Pruden A, Pei R, Storteboom H, Carlson KH (2006) Antibiotic resistance genes as emerging contaminants: studies in northern Colorado. Environ Sci Technol 40:7445–7450

    Article  CAS  Google Scholar 

  • Qiu Z, Yu Y, Chen Z, Jin M, Yang D, Zhao Z, Wang J, Shen Z, Wang X, Qian D (2012) Nanoalumina promotes the horizontal transfer of multiresistance genes mediated by plasmids across genera. Proc Natl Acad Sci U S A 109:4944–4949

    Article  Google Scholar 

  • Recchia GD, Hall RM (1995) Gene cassettes: a new class of mobile element. Microbiology 141 ( Pt 12:3015–3027

    Article  CAS  Google Scholar 

  • Ruan T, Song S, Wang T, Liu R, Lin Y, Jiang G (2014) Identification and composition of emerging quaternary ammonium compounds in municipal sewage sludge in China. Environ Sci Technol 48:4289–4297

    Article  CAS  Google Scholar 

  • Sentchilo V, Mayer AP, Guy L, Miyazaki R, Tringe SG, Barry K, Malfatti S, Goessmann A, Robinson-Rechavi M, van der Meer JR (2013) Community-wide plasmid gene mobilization and selection. ISME J. 7(6):1173–1186

    Article  CAS  Google Scholar 

  • Singer RS, Finch R, Wegener HC, Bywater R, Walters J, Lipsitch M (2003) Antibiotic resistance—the interplay between antibiotic use in animals and human beings. Lancet Infect Dis 3:47–51

    Article  Google Scholar 

  • Su JQ, Wei B, Ouyang WY, Huang FY, Zhao Y, Xu HJ, Zhu YG (2015) Antibiotic resistome and its association with bacterial communities during sewage sludge composting. Environ Sci Technol 49(12):7356–7363

    Article  CAS  Google Scholar 

  • Tabata A, Nagamune H, Maeda T, Murakami K, Miyake Y, Kourai H (2003) Correlation between resistance of Pseudomonas aeruginosa to quaternary ammonium compounds and expression of outer membrane protein OprR. Antimicrob Agents Chemother 47:2093–2099

    Article  CAS  Google Scholar 

  • Tezel U, Pierson JA, Pavlostathis SG (2006) Fate and effect of quaternaryammonium compounds on a mixed methanogenic culture. Water Res 40:3660–3668

    Article  CAS  Google Scholar 

  • Tezel U, Pierson JA, Pavlostathis SG (2007) Effect of polyelectrolytes and quaternary ammonium compounds on the anaerobic biological treatment of poultry processing wastewater. Water Res 41:1334–1342

    Article  CAS  Google Scholar 

  • Van dVA, Lorgeoux C, Gromaire MC, Chebbo G (2012) Analysis of quaternary ammonium compounds in urban stormwater samples. Environ Pollut 164:150

    Article  CAS  Google Scholar 

  • Waters VL (2001) Conjugation between bacterial and mammalian cells. Nat Genet 29:375–376

    Article  CAS  Google Scholar 

  • Weisburg WG, Barns SM, Pelletier DA, Lane DJ (1991) 16S ribosomal DNA amplification for phylogenetic study. J Bacteriol 173:697–703

    Article  CAS  Google Scholar 

  • Wistrand-Yuen E, Knopp M, Hjort K, Koskiniemi S, Berg OG, Andersson DI (2018) Evolution of high-level resistance during low-level antibiotic exposure. Nat Commun 9(1):1599

    Article  CAS  Google Scholar 

  • Yong D, Toleman MA, Giske CG, Cho HS, Sundman K, Lee K, Walsh TR (2009) Characterization of a new metallo-β-lactamase gene, blaNDM-1, and a novel erythromycin esterase gene carried on a unique genetic structure in Klebsiella pneumoniae sequence type 14 from India. Antimicrob Agents Chemother 53:5046–5054

    Article  CAS  Google Scholar 

  • Zhang Y, Gu AZ, He M, Li D, Chen J (2017) Subinhibitory concentrations of disinfectants promote the horizontal transfer of multidrug resistance genes within and across genera. Environ Sci Technol 51:570–580

    Article  CAS  Google Scholar 

  • Zheng J, Gao R, Wei Y, Chen T, Fan J, Zhou Z, Makimilua TB, Jiao Y, Chen H (2017) High-throughput profiling and analysis of antibiotic resistance genes in east Tiaoxi River. China Environ Pollut 230:648–654

    Article  CAS  Google Scholar 

  • Zhou ZC, Zheng J, Wei YY, Chen T, Dahlgren RA, Shang X, Chen H (2017) Antibiotic resistance genes in an urban river as impacted by bacterial community and physicochemical parameters. Environ Sci Pollut Res:1–10

  • Zhou ZC, Feng WQ, Han Y, Zheng J, Chen T, Wei Y-Y, Gillings M, Zhu Y-G, Chen H (2018) Prevalence and transmission of antibiotic resistance and microbiota between humans and water environments. Environ Int 121:1155–1161

    Article  CAS  Google Scholar 

  • Zhu YG, Zhao Y, Li B, Huang CL, Zhang SY, Yu S, Chen YS, Zhang T, Gillings MR, Su JQ (2017) Continental-scale pollution of estuaries with antibiotic resistance genes. Nat Microbiol 2:16270

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by Natural Science Foundation of China (21677121 and 41571130064).

Author information

Author notes

  1. Yue Han and Zhen-Chao Zhou contributed equally to this work.

Authors and Affiliations

  1. Institute of Environmental Technology, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou, 310058, China

    Yue Han, Zhen-Chao Zhou, Lin Zhu, Yuan-Yuan Wei, Wan-Qiu Feng, Lan Xu, Yang Liu, Ze-Jun Lin, Xin-Yi Shuai, Zhi-Jian Zhang & Hong Chen

Authors
  1. Yue Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zhen-Chao Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lin Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yuan-Yuan Wei
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Wan-Qiu Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Lan Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yang Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ze-Jun Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Xin-Yi Shuai
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Zhi-Jian Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Hong Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hong Chen.

Additional information

Responsible editor: Diane Purchase

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

ESM 1

(DOCX 6274 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Han, Y., Zhou, ZC., Zhu, L. et al. The impact and mechanism of quaternary ammonium compounds on the transmission of antibiotic resistance genes. Environ Sci Pollut Res 26, 28352–28360 (2019). https://doi.org/10.1007/s11356-019-05673-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11356-019-05673-2

Keywords

Search

Navigation