Abstract
Antimicrobial resistance is a major global public health problem, with fluoroquinolone-resistant strains of Escherichia coli posing a significant threat. This study examines the genetic characterization of ESBL-producing E. coli isolates in Mexican hospitals, which are resistant to both cephalosporins and fluoroquinolones. A total of 23 ESBL-producing E. coli isolates were found to be positive for the qepA gene, which confers resistance to fluoroquinolones. These isolates exhibited drug resistance phenotypes and belonged to specific sequence types and phylogenetic groups. The genetic context of the qepA gene was identified in a novel genetic context flanked by IS26 sequences. Mating experiments showed the co-transfer of qepA1 and chrA determinants alongside blaCTX-M-15 genes, emphasizing the potential for these genetic structures to spread among Enterobacterales. The emergence of multidrug-resistant Gram-negative bacteria carrying these resistance genes is a significant clinical concern for public healthcare systems.
Similar content being viewed by others
References
Pokharel S, Raut S, Adhikari B (2019) Tackling antimicrobial resistance in low-income and middle-income countries. BMJ Glob Health 4(6):e002104. https://doi.org/10.1136/bmjgh-2019-002104
Vieira DC, Lima WG, de Paiva MC (2020) Plasmid-mediated quinolone resistance (PMQR) among Enterobacteriales in Latin America: a systematic review. Mol Biol Rep 47(2):1471–1483. https://doi.org/10.1007/s11033-019-05220-9
Larramendy S, Deglaire V, Dusollier P, Fournier JP, Caillon J, Beaudeau F, Moret L (2020) Risk factors of extended-spectrum beta-lactamases-producing Escherichia coli community acquired urinary tract infections: a systematic review. Infect Drug Resist 3(13):3945–3955. https://doi.org/10.2147/IDR.S269033
Tandogdu Z, Wagenlehner FM (2016) Global epidemiology of urinary tract infections. Curr Opin Infect Dis 29(1):73–79. https://doi.org/10.1097/QCO.0000000000000228
Daneman N, Chateau D, Dahl M, Zhang J, Fisher A, Sketris IS, Quail J, Marra F, Ernst P, Bugden S (2020) Canadian Network for Observational Drug Effect Studies (CNODES) Investigators. Fluoroquinolone use for uncomplicated urinary tract infections in women: a retrospective cohort study. Clin Microbiol Infect 26(5):613–618. https://doi.org/10.1016/j.cmi.2019.10.016
Bader MS, Hawboldt J, Brooks A (2010) Management of complicated urinary tract infections in the era of antimicrobial resistance. Postgrad Med 122(6):7–15. https://doi.org/10.3810/pgm.2010.11.2217
Kawamura K, Nagano N, Suzuki M, Wachino JI, Kimura K, Arakawa Y (2017) ESBL-producing Escherichia coli and its rapid rise among healthy people. Food Saf (Tokyo) 5(4):122–150. https://doi.org/10.14252/foodsafetyfscj.2017011
Rincón G, Radice M, Giovanakis M, Di Conza JA, Gutkind G (2014) First report of plasmid-mediated fluoroquinolone efflux pump QepA in Escherichia coli clinical isolate ST68 in South America. Diagn Microbiol Infect Dis 79(1):70–72. https://doi.org/10.1016/j.diagmicrobio.2014.01.007
Hooper DC, Jacoby GA (2015) Mechanisms of drug resistance: quinolone resistance. Ann N Y Acad Sci 1354(1):12–31. https://doi.org/10.1111/nyas.12830
Poirel L, Cattoir V, Nordmann P (2008) Is plasmid-mediated quinolone resistance a clinically significant problem? Clin Microbiol Infect 14(4):295–297. https://doi.org/10.1111/j.1469-0691.2007.01930.x
Yamane K, Wachino J, Suzuki S, Kimura K, Shibata N, Kato H, Shibayama K, Konda T, Arakawa Y (2007) New plasmid-mediated fluoroquinolone efflux pump, QepA, found in an Escherichia coli clinical isolate. Antimicrob Agents Chemother 51(9):3354–3360. https://doi.org/10.1128/AAC.00339-07
Périchon B, Bogaerts P, Lambert T, Frangeul L, Courvalin P, Galimand M (2008) Sequence of conjugative plasmid pIP1206 mediating resistance to aminoglycosides by 16S rRNA methylation and to hydrophilic fluoroquinolones by efflux. Antimicrob Agents Chemother 52(7):2581–2592. https://doi.org/10.1128/AAC.01540-07
Cattoir V, Poirel L, Nordmann P (2008) Plasmid-mediated quinolone resistance pump QepA2 in an Escherichia coli isolate from France. Antimicrob Agents Chemother 52(10):3801–3804. https://doi.org/10.1128/AAC.00638-08
Clinical and Laboratory Standards Institute. Clinical and Laboratory Standards Institute; Wayne, PA: 2017. Performance standard for antimicrobial susceptibility testing. CLSI supplement M100.
Silva-Sanchez J, Barrios H, Reyna-Flores F, Bello-Diaz M, Sanchez-Perez A, Rojas T, Bacterial Resistance Consortium, Garza-Ramos U (2011) Prevalence and characterization of plasmid-mediated quinolone resistance genes in extended-spectrum β-lactamase-producing Enterobacteriaceae isolates in Mexico. Microb Drug Resist 17(4):497–505. https://doi.org/10.1089/mdr.2011.0086
Cattoir V, Poirel L, Rotimi V, Soussy CJ, Nordmann P (2007) Multiplex PCR for detection of plasmid-mediated quinolone resistance qnr genes in ESBL-producing enterobacterial isolates. J Antimicrob Chemother 60(2):394–397. https://doi.org/10.1093/jac/dkm204
Clermont O, Bonacorsi S, Bingen E (2000) Rapid and simple determination of the Escherichia coli phylogenetic group. Appl Environ Microbiol 66:4555–4558. https://doi.org/10.1128/AEM.66.10.4555-4558.2000
Betancor L, Schelotto F, Martinez A, Pereira M, Algorta G, Rodríguez MA, Vignoli R, Chabalgoity JA (2004) Random amplified polymorphic DNA and phenotyping analysis of Salmonella enterica serovar enteritidis isolates collected from humans and poultry in Uruguay from 1995 to 2002. J Clin Microbiol 42(3):1155–1162. https://doi.org/10.1128/JCM.42.3.1155-1162.2004
Wirth T, Falush D, Lan R, Colles F, Mensa P, Wieler LH, Karch H, Reeves PR, Maiden MC, Ochman H, Achtman M (2006 Jun) Sex and virulence in Escherichia coli: an evolutionary perspective. Mol Microbiol 60(5):1136–1151. https://doi.org/10.1111/j.1365-2958.2006.05172.x
Miller JH. Experiments in molecular genetics. (1972) Cold Spring Harbor, N.Y: Cold Spring Harbor Laboratory. xvi, 466 p. p
Kieser T (1984) Factors affecting the isolation of CCC DNA from Streptomyces lividans and Escherichia coli. Plasmid 12(1):19–36. https://doi.org/10.1016/0147-619x(84)90063-5
Carattoli A, Bertini A, Villa L, Falbo V, Hopkins KL, Threlfall EJ (2005) Identification of plasmids by PCR-based replicon typing. J Microbiol Methods 63(3):219–228. https://doi.org/10.1016/j.mimet.2005.03.018
Carattoli A, Zankari E, García-Fernández A, Voldby Larsen M, Lund O, Villa L, Møller Aarestrup F, Hasman H (2014) In silico detection and typing of plasmids using PlasmidFinder and plasmid multilocus sequence typing. Antimicrob Agents Chemother 58(7):3895–3903. https://doi.org/10.1128/AAC.02412-14
Elshamy AA, Aboshanab KM, Yassien MA, Hassouna NA (2020 Mar) Prevalence of plasmid-mediated resistance genes among multidrug-resistant uropathogens in Egypt. Afr Health Sci 20(1):190–198. https://doi.org/10.4314/ahs.v20i1.241
Perez-Lopez A, Sundararaju S, Al-Mana H, Tsui KM, Hasan MR, Suleiman M, Janahi M, Al Maslamani E, Tang P (2020) Molecular characterization of extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae among the pediatric population in Qatar. Front Microbiol 11:581711. https://doi.org/10.3389/fmicb.2020.581711
Azargun R, Sadeghi MR, Soroush Barhaghi MH, Samadi Kafil H, Yeganeh F, Ahangar Oskouee M, Ghotaslou R (2018) The prevalence of plasmid-mediated quinolone resistance and ESBL-production in Enterobacteriaceae isolated from urinary tract infections. Infect Drug Resist 23(11):1007–1014. https://doi.org/10.2147/IDR.S160720
Fu Y, Zhang W, Wang H, Zhao S, Chen Y, Meng F, Zhang Y, Xu H, Chen X, Zhang F (2013) Specific patterns of gyrA mutations determine the resistance difference to ciprofloxacin and levofloxacin in Klebsiella pneumoniae and Escherichia coli. BMC Infect Dis 7(13):8. https://doi.org/10.1186/1471-2334-13-8
Roy Chowdhury P, McKinnon J, Liu M, Djordjevic SP (2019) Multidrug resistant uropathogenic Escherichia coli ST405 with a novel, composite IS26 transposon in a unique chromosomal location. Front Microbiol 8(9):3212. https://doi.org/10.3389/fmicb.2018.03212
Reyna-Flores F, Barrios H, Garza-Ramos U, Sánchez-Pérez A, Rojas-Moreno T, Uribe-Salas FJ, Fagundo-Sierra R, Silva-Sanchez J (2013) Molecular epidemiology of Escherichia coli O25b-ST131 isolates causing community-acquired UTIs in Mexico. Diagn Microbiol Infect Dis 76(3):396–398. https://doi.org/10.1016/j.diagmicrobio.2013.03.026
Silva-Sánchez J, Cruz-Trujillo E, Barrios H, Reyna-Flores F, Sánchez-Pérez A, Bacterial Resistance Consortium, Garza-Ramos U (2013) Characterization of plasmid-mediated quinolone resistance (PMQR) genes in extended-spectrum β-lactamase-producing Enterobacteriaceae pediatric clinical isolates in Mexico. PLoS One 8(10):e77968. https://doi.org/10.1371/journal.pone.0077968
Kim ES, Jeong JY, Choi SH, Lee SO, Kim SH, Kim MN, Woo JH, Kim YS (2009) Plasmid-mediated fluoroquinolone efflux pump gene, qepA, in Escherichia coli clinical isolates in Korea. Diagn Microbiol Infect Dis 65(3):335–338. https://doi.org/10.1016/j.diagmicrobio.2009.07.006
Aguilar-Barajas E, Paluscio E, Cervantes C, Rensing C (2008) Expression of chromate resistance genes from Shewanella sp. strain ANA-3 in Escherichia coli. FEMS Microbiol Lett 285(1):97–100. https://doi.org/10.1111/j.1574-6968.2008.01220.x
Caballero-Flores GG, Acosta-Navarrete YM, Ramírez-Díaz MI, Silva-Sánchez J, Cervantes C (2012) Chromate-resistance genes in plasmids from antibiotic-resistant nosocomial enterobacterial isolates. FEMS Microbiol Lett 327(2):148–154. https://doi.org/10.1111/j.1574-6968.2011.02473.x
Chen X, He L, Li Y, Zeng Z, Deng Y, Liu Y, Liu JH (2014) Complete sequence of a F2:A-:B- plasmid pHN3A11 carrying rmtB and qepA, and its dissemination in China. Vet Microbiol 174(1-2):267–271. https://doi.org/10.1016/j.vetmic.2014.08.023
Acknowledgements
Bacterial Resistance Consortium: Carpermor, Laboratorio de Referencia Internacional, Cd de México. Felipe J. Uribe-Salas; ISTE-S, ISSSTESON, Hermosillo, Sonora. M.C. Moisés Navarro; Instituto Nacional de Cancerología (INCan), Cd de México. Dra. Patricia Cornejo-Juárez; Sanatorio Durango (SD-DF), Cd de México. Dr. Octavio Novoa-Farías; Hospital de Pediatría, Centro Médico Nacional Siglo XXI; Ciudad de México. Dr. Fortino Solórzano; Hospital Regional de Alta Especialidad, Oaxaca, Q. Sofía Cruz
Funding
This work was supported by grant 256988 from SEP-CONACyT (Secretaría de Educación Pública, Consejo Nacional de Ciencia y Tecnología).
Author information
Authors and Affiliations
Consortia
Contributions
Conceptualization: HBC, JSS, UGR; methodology: HBC, JDB, LL, FRF, ASP; writing—original draft preparation: HBC, JDB; writing—review and editing: HBC, JDB, UGR; funding acquisition: JSS; supervision: HBC.
Corresponding author
Ethics declarations
Conflict of interest
The authors declare no competing interests.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Responsible Editor: Beatriz Ernestina Cabilio Guth
Supplementary information
ESM 1
(PNG 32 kb)
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Duran-Bedolla, J., Garza-Ramos, U., Silva-Sánchez, J. et al. Genetic characterization of plasmid-mediated fluoroquinolone efflux pump QepA among ESBL-producing Escherichia coli isolates in Mexico. Braz J Microbiol 54, 2791–2797 (2023). https://doi.org/10.1007/s42770-023-01115-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s42770-023-01115-x