Abstract
The global dissemination of antibiotic resistance is severely threatening public health. Several non-antibiotic chemicals facilitate the horizontal transfer of antibiotic resistance genes. Bisphenol analogs, e.g., bisphenol S and bisphenol AF, are known pollutants, yet their effects on the propagation and spread of antibiotic resistance genes remain unknown. Our study demonstrates for the first time that bisphenol S and bisphenol AF at environmentally relevant concentrations of 0.1–100.0 μg/L accelerates 2–5 folds the conjugative transfer frequency of RP4 plasmid-borne antibiotic resistance genes within and across bacterial genera, from Escherichia coli DH5α to Escherichia coli HB101 or Salmonella enterica. Bisphenol S and bisphenol AF exerted no effect on the bacterial growth and little change in cell membrane permeability. Accelerated conjugative transfer is explained by the repression of the global regulator, with a maximum relative expression level of 0.23, and of the vertical transfer system (0.26), with simultaneous up-regulation of DNA horizontal transfer and replication system (3.66). This bisphenols-induced conjugative transfer of antibiotic resistance genes could promote the spread of antibiotic resistance in the environment and in gut microbial communities of wildlife and human.
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References
Barth PT, Ellis K, Bechhofer DH, Figurski DH (1984) Involvement of kil and kor genes in the phenotype of a host-range mutant of RP4. Mol Gen Genet 197:236–243. https://doi.org/10.1007/BF00330969
Bengtsson-Palme J, Kristiansson E, Larsson DJ (2018) Environmental factors influencing the development and spread of antibiotic resistance. FEMS Microbiol Rev 42:68–80. https://doi.org/10.1093/femsre/fux053
Catenza CJ, Farooq A, Shubear NS, Donkor KK (2021) A targeted review on fate, occurrence, risk and health implications of bisphenol analogues. Chemosphere 268:129273. https://doi.org/10.1016/j.chemosphere.2020.129273
Cen T, Zhang X, Xie S, Li D (2020) Preservatives accelerate the horizontal transfer of plasmid-mediated antimicrobial resistance genes via differential mechanisms. Environ Int 138:105544. https://doi.org/10.1016/j.envint.2020.105544
Che Y, Yang Y, Xu X et al (2021) Conjugative plasmids interact with insertion sequences to shape the horizontal transfer of antimicrobial resistance genes. Proc Natl Acad Sci USA 118:e2008731118. https://doi.org/10.1073/pnas.2008731118
Chen D, Kannan K, Tan H et al (2016) Bisphenol analogues other than BPA: environmental occurrence, human exposure, and toxicity - A review. Environ Sci Technol 50:5438–5453. https://doi.org/10.1021/acs.est.5b05387
Feng D, Zhang H, Jiang X et al (2020) Bisphenol A exposure induces gut microbiota dysbiosis and consequent activation of gut-liver axis leading to hepatic steatosis in CD-1 mice. Environ Pollut 265:114880. https://doi.org/10.1016/j.envpol.2020.114880
Feng G, Huang H, Chen Y (2021) Effects of emerging pollutants on the occurrence and transfer of antibiotic resistance genes: a review. J Hazard Mater 420:126602. https://doi.org/10.1016/j.jhazmat.2021.126602
Groussin M, Poyet M, Sistiaga A et al (2021) Elevated rates of horizontal gene transfer in the industrialized human microbiome. Cell 184:2053–2067. https://doi.org/10.1016/j.cell.2021.02.052
Ji Q, Zhang C, Li D (2020) Influences and mechanisms of nanofullerene on the horizontal transfer of plasmid-encoded antibiotic resistance genes between E. coli strains. Front Environ Sci Eng 14:1–10. https://doi.org/10.1007/s11783-020-1287-0
Jin H, Xie J, Mao L et al (2020) Bisphenol analogue concentrations in human breast milk and their associations with postnatal infant growth. Environ Pollut 259:113779. https://doi.org/10.1016/j.envpol.2019.113779
Jin H, Zhu J, Chen Z et al (2018) Occurrence and partitioning of bisphenol analogues in adults’ blood from China. Environ Sci Technol 52:812–820. https://doi.org/10.1021/acs.est.7b03958
Jong MC, Harwood CR, Blackburn A et al (2020) Impact of redox conditions on antibiotic resistance conjugative gene transfer frequency and plasmid fate in wastewater ecosystems. Environ Sci Technol 54:14984–14993. https://doi.org/10.1021/acs.est.0c03714
Ledingham K, Hinchliffe S, Jackson M et al (2019) Antibiotic resistance: using a cultural contexts of health approach to address a global health challenge. WHO Reg off Eur 29:1–39
Li G, Chen X, Yin H et al (2020) Natural sphalerite nanoparticles can accelerate horizontal transfer of plasmid-mediated antibiotic-resistance genes. Environ Int 136:105497. https://doi.org/10.1016/j.envint.2020.105497
Lin H, Ye C, Chen S et al (2017) Viable but non-culturable E. coli induced by low level chlorination have higher persistence to antibiotics than their culturable counterparts. Environ Pollut 230:242–249. https://doi.org/10.1016/j.envpol.2017.06.047
Liu J, Zhang L, Lu G et al (2021) Occurrence, toxicity and ecological risk of Bisphenol A analogues in aquatic environment – A review. Ecotoxicol Environ Saf 208:111481. https://doi.org/10.1016/j.ecoenv.2020.111481
Liu M, Jia S, Dong T et al (2020) Metabolomic and transcriptomic analysis of mcf-7 cells exposed to 23 chemicals at human-relevant levels: estimation of individual chemical contribution to effects. Environ Health Perspect 128:127008-1-127008–16. https://doi.org/10.1289/EHP6641
Lu J, Guo J (2021) Disinfection spreads antimicrobial resistance. Science 371:474
Lu J, Wang Y, Jin M et al (2020) Both silver ions and silver nanoparticles facilitate the horizontal transfer of plasmid-mediated antibiotic resistance genes. Water Res. https://doi.org/10.1016/j.watres.2019.115229
Lu J, Wang Y, Li J et al (2018) Triclosan at environmentally relevant concentrations promotes horizontal transfer of multidrug resistance genes within and across bacterial genera. Environ Int 121:1217–1226. https://doi.org/10.1016/j.envint.2018.10.040
Luo Y, Wang Q, Lu Q et al (2014) An ionic liquid facilitates the proliferation of antibiotic resistance genes mediated by class I integrons. Environ Sci Technol Lett 1:266–270. https://doi.org/10.1021/ez500103v
Mao J, Jain A, Denslow ND et al (2020) Bisphenol A and bisphenol S disruptions of the mouse placenta and potential effects on the placenta-brain axis. Proc Natl Acad Sci USA 117:4642–4652. https://doi.org/10.1073/pnas.1919563117
McDonough CM, Xu HS, Guo TL (2021) Toxicity of bisphenol analogues on the reproductive, nervous, and immune systems, and their relationships to gut microbiome and metabolism: insights from a multi-species comparison. Crit Rev Toxicol 51:283–300. https://doi.org/10.1080/10408444.2021.1908224
Noszczyńska M, Piotrowska-Seget Z (2018) Bisphenols: application, occurrence, safety, and biodegradation mediated by bacterial communities in wastewater treatment plants and rivers. Chemosphere 201:214–223. https://doi.org/10.1016/j.chemosphere.2018.02.179
Pansegrau W, Balzer D, Kruft V (1990) In vitro assembly of relaxosomes at the transfer origin of plasmid RP4. Proc Natl Acad Sci USA 87:6555–6559
Qiu W, Chen B, Greer JB et al (2020) Transcriptomic responses of bisphenol S predict involvement of immune function in the cardiotoxicity of early life-stage zebrafish (Danio rerio). Environ Sci Technol 54:2869–2877. https://doi.org/10.1021/acs.est.9b06213
Qiu Z, Shen Z, Qian D et al (2015) Effects of nano-TiO2 on antibiotic resistance transfer mediated by RP4 plasmid. Nanotoxicology 9:895–904. https://doi.org/10.3109/17435390.2014.991429
Qiu Z, Yu Y, Chen Z et al (2012) Nanoalumina promotes the horizontal transfer of multiresistance genes mediated by plasmids across genera. Proc Natl Acad Sci USA 109:4944–4949. https://doi.org/10.1073/pnas.1107254109
Rodríguez-Beltrán J, DelaFuente J, León-Sampedro R et al (2021) Beyond horizontal gene transfer: the role of plasmids in bacterial evolution. Nat Rev Microbiol 19:347–359. https://doi.org/10.1038/s41579-020-00497-1
Schröder G, Lanka E (2005) The mating pair formation system of conjugative plasmids—A versatile secretion machinery for transfer of proteins and DNA. Plasmid 54:1–25. https://doi.org/10.1016/J.PLASMID.2005.02.001
Vasiljevic T, Harner T (2021) Bisphenol A and its analogues in outdoor and indoor air: properties, sources and global levels. Sci Total Environ 789:148013. https://doi.org/10.1016/j.scitotenv.2021.148013
Wang L, Ye C, Guo L et al (2021a) Assessment of the UV/chlorine process in the disinfection of Pseudomonas aeruginosa: efficiency and mechanism. Environ Sci Technol 55:9221–9230. https://doi.org/10.1021/acs.est.1c00645
Wang Q, Mao D, Luo Y (2015) Ionic liquid facilitates the conjugative transfer of antibiotic resistance genes mediated by plasmid RP4. Environ Sci Technol 49:8731–8740. https://doi.org/10.1021/acs.est.5b01129
Wang Y, Lu J, Mao L et al (2019) Antiepileptic drug carbamazepine promotes horizontal transfer of plasmid-borne multi-antibiotic resistance genes within and across bacterial genera. ISME J 13:509–522. https://doi.org/10.1038/s41396-018-0275-x
Wang Y, Lu J, Zhang S et al (2021b) Non-antibiotic pharmaceuticals promote the transmission of multidrug resistance plasmids through intra- and intergenera conjugation. ISME J 15:2493–2508. https://doi.org/10.1038/s41396-021-00945-7
Wang Y, Wang B, Wang Q et al (2021c) Intestinal toxicity and microbial community disorder induced by bisphenol F and bisphenol S in zebrafish. Chemosphere 280:130711. https://doi.org/10.1016/j.chemosphere.2021.130711
Wu LH, Zhang XM, Wang F et al (2018) Occurrence of bisphenol S in the environment and implications for human exposure: a short review. Sci Total Environ 615:87–98. https://doi.org/10.1016/j.scitotenv.2017.09.194
Xie S, Gu AZ, Cen T et al (2019) The effect and mechanism of urban fine particulate matter (PM2.5) on horizontal transfer of plasmid-mediated antimicrobial resistance genes. Sci Total Environ 683:116–123. https://doi.org/10.1016/j.scitotenv.2019.05.115
Yu K, Chen F, Yue L et al (2020) CeO2 nanoparticles regulate the propagation of antibiotic resistance genes by altering cellular contact and plasmid transfer. Environ Sci Technol 54:10012–10021. https://doi.org/10.1021/acs.est.0c01870
Yu Z, Wang Y, Lu J et al (2021) Nonnutritive sweeteners can promote the dissemination of antibiotic resistance through conjugative gene transfer. ISME J 15:2117–2130. https://doi.org/10.1038/s41396-021-00909-x
Zhang S, Wang Y, Song H et al (2019) Copper nanoparticles and copper ions promote horizontal transfer of plasmid-mediated multi-antibiotic resistance genes across bacterial genera. Environ Int 129:478–487. https://doi.org/10.1016/j.envint.2019.05.054
Zhang Y, Gu AZ, He M et al (2017) Subinhibitory concentrations of disinfectants promote the horizontal transfer of multidrug resistance genes within and across genera. Environ Sci Technol 51:570–580. https://doi.org/10.1021/acs.est.6b03132
Zhao N, Hu H, Zhao M et al (2021) Occurrence of free-form and conjugated bisphenol analogues in marine organisms. Environ Sci Technol 55:4914–4922. https://doi.org/10.1021/acs.est.0c08458
Acknowledgements
This research was supported by Singapore-China Joint Research Grant Call (NRF-NSFC 3rd Joint Grant Call-Earth Science) (41861144023), Natural Science Foundation of China-Joint Fund Project (U2005206), Xiamen Municipal Bureau of Science and Technology (YDZX20203502000003). Also, we express our sincerest thanks to Prof. Yi Luo from Nanjing University for the provision of all three bacterial strains.
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MF: Conceptualization, Writing—Original Draft, Writing—Review & Editing, Supervision, Project administration; CY: Conceptualization, Methodology, Software, Formal analysis, Investigation, Writing—Review & Editing, Visualization, Project administration; SZ: Methodology, Software, Formal analysis, Investigation; VKS: Writing—Review & Editing, Supervision; KM: Writing—Review & Editing. XY: Resources, Supervision, Project administration, Funding acquisition.
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Feng, M., Ye, C., Zhang, S. et al. Bisphenols promote the conjugative transfer of antibiotic resistance genes without damaging cell membrane. Environ Chem Lett 20, 1553–1560 (2022). https://doi.org/10.1007/s10311-022-01397-x
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DOI: https://doi.org/10.1007/s10311-022-01397-x