{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T00:16:25Z","timestamp":1792109785337,"version":"4.4.0"},"reference-count":128,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,8,6]],"date-time":"2022-08-06T00:00:00Z","timestamp":1659744000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004442","name":"National Science Centre","doi-asserted-by":"publisher","award":["2019\/35\/B\/NZ6\/03996"],"award-info":[{"award-number":["2019\/35\/B\/NZ6\/03996"]}],"id":[{"id":"10.13039\/501100004442","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>The rapid emergence of multidrug-resistant (MDR) bacteria indisputably constitutes a major global health problem. Pathogenic Escherichia coli are listed among the most critical group of bacteria that require fast development of new antibiotics and innovative treatment strategies. Among harmful extraintestinal Enterobacteriaceae strains, uropathogenic E. coli (UPEC) pose a significant health threat. UPEC are considered the major causative factor of urinary tract infection (UTI), the second-most commonly diagnosed infectious disease in humans worldwide. UTI treatment places a substantial financial burden on healthcare systems. Most importantly, the misuse of antibiotics during treatment has caused selection of strains with the ability to acquire MDR via miscellaneous mechanisms resulting in gaining resistance against many commonly prescribed antibiotics like ampicillin, gentamicin, cotrimoxazole and quinolones. Mobile genetic elements (MGEs) such as transposons, integrons and conjugative plasmids are the major drivers in spreading resistance genes in UPEC. The co-occurrence of various bacterial evasion strategies involving MGEs and the SOS stress response system requires further research and can potentially lead to the discovery of new, much-awaited therapeutic targets. Here, we analyzed and summarized recent discoveries regarding the role, mechanisms, and perspectives of MDR in the pathogenicity of UPEC.<\/jats:p>","DOI":"10.3390\/genes13081397","type":"journal-article","created":{"date-parts":[[2022,8,7]],"date-time":"2022-08-07T22:51:46Z","timestamp":1659912706000},"page":"1397","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":70,"title":["Molecular Factors and Mechanisms Driving Multidrug Resistance in Uropathogenic Escherichia coli\u2014An Update"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6073-1866","authenticated-orcid":false,"given":"Marcin","family":"Rozwadowski","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Bielanski Hospital, Ceglowska 80, 01-809 Warsaw, Poland"},{"name":"Department of Cell Biology and Immunology, Centre of Postgraduate Medical Education, 01-813 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1270-5505","authenticated-orcid":false,"given":"Damian","family":"Gawel","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Immunology, Centre of Postgraduate Medical Education, 01-813 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1038\/nrmicro1810","article-title":"In appreciation of Theodor Escherich","volume":"5","author":"Hacker","year":"2007","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e05826","DOI":"10.7554\/eLife.05826","article-title":"The unexhausted potential of E. coli","volume":"4","author":"Blount","year":"2015","journal-title":"Elife"},{"key":"ref_3","first-page":"77","article-title":"Escherichia coli as a model system to study DNA repair genes of eukaryotic organisms","volume":"2","author":"Silva","year":"2003","journal-title":"Genet. Mol. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"S692","DOI":"10.1093\/clinids\/5.Supplement_4.S692","article-title":"Classification of pathogenic Escherichia coli according to serotype and the production of virulence factors, with special reference to colonization-factor antigens","volume":"5","author":"Evans","year":"1983","journal-title":"Rev. Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1111\/j.1574-6976.2006.00016.x","article-title":"The structures of Escherichia coli O-polysaccharide antigens","volume":"30","author":"Stenutz","year":"2006","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"10593","DOI":"10.1074\/jbc.REV120.009402","article-title":"Lipopolysaccharide O-antigens-bacterial glycans made to measure","volume":"295","author":"Whitfield","year":"2020","journal-title":"J. Biol. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s13099-019-0290-0","article-title":"Virulence factors, prevalence and potential transmission of extraintestinal pathogenic Escherichia coli isolated from different sources: Recent reports","volume":"11","author":"Sarowska","year":"2019","journal-title":"Gut Pathog."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e00135-18","DOI":"10.1128\/CMR.00135-18","article-title":"Global Extraintestinal Pathogenic Escherichia coli (ExPEC) Lineages","volume":"32","author":"Manges","year":"2019","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2680","DOI":"10.1128\/AAC.02897-15","article-title":"Antibiotic Resistance among Urinary Isolates from Female Outpatients in the United States in 2003 and 2012","volume":"60","author":"Sanchez","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1566","DOI":"10.3389\/fmicb.2017.01566","article-title":"UroPathogenic Escherichia coli (UPEC) Infections: Virulence Factors, Bladder Responses, Antibiotic, and Non-antibiotic Antimicrobial Strategies","volume":"8","author":"Terlizzi","year":"2017","journal-title":"Front. Microbiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/nrmicro3432","article-title":"Urinary tract infections: Epidemiology, mechanisms of infection and treatment options","volume":"13","author":"Walker","year":"2015","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1067\/mda.2003.7","article-title":"Epidemiology of urinary tract infections: Incidence, morbidity, and economic costs","volume":"49","author":"Foxman","year":"2003","journal-title":"Dis. Mon."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1756287219832172","DOI":"10.1177\/1756287219832172","article-title":"An introduction to the epidemiology and burden of urinary tract infections","volume":"11","author":"Medina","year":"2019","journal-title":"Ther. Adv. Urol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1056\/NEJM199608153350703","article-title":"A prospective study of risk factors for symptomatic urinary tract infection in young women","volume":"335","author":"Hooton","year":"1996","journal-title":"N. Engl. J. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"359","DOI":"10.12816\/0003256","article-title":"Recurrent Urinary Tract Infections Management in Women: A review","volume":"13","year":"2013","journal-title":"Sultan Qaboos Univ. Med. J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.idc.2013.09.003","article-title":"Urinary tract infection syndromes: Occurrence, recurrence, bacteriology, risk factors, and disease burden","volume":"28","author":"Foxman","year":"2014","journal-title":"Infect. Dis. Clin. N. Am."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"20","DOI":"10.3345\/kjp.2015.58.1.20","article-title":"Molecular typing of uropathogenic Escherichia coli isolated from Korean children with urinary tract infection","volume":"58","author":"Yun","year":"2015","journal-title":"Korean J. Pediatr."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"146","DOI":"10.3389\/fmicb.2017.00146","article-title":"Virulence Markers and Phylogenetic Analysis of Escherichia coli Strains with Hybrid EAEC\/UPEC Genotypes Recovered from Sporadic Cases of Extraintestinal Infections","volume":"8","author":"Lara","year":"2017","journal-title":"Front. Microbiol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Dadi, B.R., Abebe, T., Zhang, L., Mihret, A., Abebe, W., and Amogne, W. (2020). Distribution of virulence genes and phylogenetics of uropathogenic Escherichia coli among urinary tract infection patients in Addis Ababa, Ethiopia. BMC Infect. Dis., 20.","DOI":"10.1186\/s12879-020-4844-z"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.2147\/IDR.S248572","article-title":"Characterization of Extended-Spectrum beta-Lactamase-Producing Uropathogenic Escherichia coli Among Iranian Kidney Transplant Patients","volume":"13","author":"Halaji","year":"2020","journal-title":"Infect. Drug Resist."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"707","DOI":"10.2147\/IDR.S163979","article-title":"Epidemiology, susceptibility, and risk factors for acquisition of MDR\/XDR Gram-negative bacteria among kidney transplant recipients with urinary tract infections","volume":"11","author":"Yuan","year":"2018","journal-title":"Infect. Drug Resist."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1097\/01.ju.0000152365.43125.3b","article-title":"Urologic diseases in America Project: Analytical methods and principal findings","volume":"173","author":"Litwin","year":"2005","journal-title":"J. Urol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1073\/pnas.0308125100","article-title":"Differentiation and developmental pathways of uropathogenic Escherichia coli in urinary tract pathogenesis","volume":"101","author":"Justice","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"13803","DOI":"10.1038\/ncomms13803","article-title":"A diverse intrinsic antibiotic resistome from a cave bacterium","volume":"7","author":"Pawlowski","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Yang, W., Liu, P., Chen, Y., Lv, Q., Wang, Z., Huang, W., Jiang, H., Zheng, Y., Jiang, Y., and Sun, L. (2022). Dictamnine Inhibits the Adhesion to and Invasion of Uropathogenic Escherichia coli (UPEC) to Urothelial Cells. Molecules, 27.","DOI":"10.3390\/molecules27010272"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"112889","DOI":"10.1016\/j.jep.2020.112889","article-title":"Antiadhesive natural products against uropathogenic E. coli: What can we learn from cranberry extract?","volume":"257","author":"Scharf","year":"2020","journal-title":"J. Ethnopharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.3389\/fmicb.2020.01509","article-title":"Alternative Therapeutic Options to Antibiotics for the Treatment of Urinary Tract Infections","volume":"11","author":"Loubet","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1111\/j.1365-2672.2006.02857.x","article-title":"Antagonistic activity of probiotic lactobacilli and bifidobacteria against entero- and uropathogens","volume":"100","author":"Hutt","year":"2006","journal-title":"J. Appl. Microbiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1111\/j.1574-695X.2001.tb01549.x","article-title":"Oral probiotics can resolve urogenital infections","volume":"30","author":"Reid","year":"2001","journal-title":"FEMS Immunol. Med. Microbiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1111\/j.1469-0691.2011.03570.x","article-title":"Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: An international expert proposal for interim standard definitions for acquired resistance","volume":"18","author":"Magiorakos","year":"2012","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_31","first-page":"1114","article-title":"Significance of Regional Antibiogram and MDR of ESBL Producing Uropathogens Infecting Non-hospitalized Patients","volume":"7","author":"Rishabh","year":"2018","journal-title":"Gurugram. Int. J. Curr. Microbiol."},{"key":"ref_32","first-page":"2643","article-title":"Study of class 1 integrons and plasmid profile among multiple drug resistant uropathogenic Escherichia coli","volume":"33","author":"Javed","year":"2020","journal-title":"Pak. J. Pharm. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.apjtb.2015.09.022","article-title":"Prevalence of multi-drug resistant uropathogenic Escherichia coli in Potohar region of Pakistan","volume":"6","author":"Ali","year":"2016","journal-title":"Asian Pac. J.Trop. Biomed."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Contreras-Alvarado, L.M., Zavala-Vega, S., Cruz-Cordova, A., Reyes-Grajeda, J.P., Escalona-Venegas, G., Flores, V., Alcazar-Lopez, V., Arellano-Galindo, J., Hernandez-Castro, R., and Castro-Escarpulli, G. (2021). Molecular Epidemiology of Multidrug-Resistant Uropathogenic Escherichia coli O25b Strains Associated with Complicated Urinary Tract Infection in Children. Microorganisms, 9.","DOI":"10.3390\/microorganisms9112299"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"19","DOI":"10.7883\/yoken.JJID.2015.652","article-title":"Epidemiology of Multidrug Resistant Uropathogenic Escherichia coli in Iran: A Systematic Review and Meta-Analysis","volume":"70","author":"Hadifar","year":"2017","journal-title":"Jpn. J. Infect. Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/s12941-018-0286-5","article-title":"An evaluation of multidrug-resistant Escherichia coli isolates in urinary tract infections from Aguascalientes, Mexico: Cross-sectional study","volume":"17","author":"Harel","year":"2018","journal-title":"Ann. Clin. Microbiol. Antimicrob."},{"key":"ref_37","first-page":"25","article-title":"Frequency of hlyA, hlyB, hlyC and hlyD genes in uropathogenic Escherichia coli isolated from UTI patients in Shiraz","volume":"16","author":"Moeinizadeh","year":"2021","journal-title":"GMS Hyg. Infect. Control"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"415","DOI":"10.2147\/IDR.S287792","article-title":"Encouraging the Development of New Antibiotics: Are Financial Incentives the Right Way Forward? A Systematic Review and Case Study","volume":"14","author":"Dutescu","year":"2021","journal-title":"Infect. Drug Resist."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/s13756-016-0154-z","article-title":"Estimating the morbidity and mortality associated with infections due to multidrug-resistant bacteria (MDRB), France, 2012","volume":"5","author":"Lacoste","year":"2016","journal-title":"Antimicrob. Resist. Infect. Control"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1038\/s41598-020-79754-5","article-title":"First report on antibiotic resistance and antimicrobial activity of bacterial isolates from 13,000-year old cave ice core","volume":"11","author":"Paun","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1126\/science.1176950","article-title":"Functional characterization of the antibiotic resistance reservoir in the human microflora","volume":"325","author":"Sommer","year":"2009","journal-title":"Science"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.ijmm.2013.02.009","article-title":"Intrinsic antibiotic resistance: Mechanisms, origins, challenges and solutions","volume":"303","author":"Cox","year":"2013","journal-title":"Int. J. Med. Microbiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1128\/jb.153.1.232-240.1983","article-title":"Porin channels in Escherichia coli: Studies with beta-lactams in intact cells","volume":"153","author":"Nikaido","year":"1983","journal-title":"J. Bacteriol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1042\/EBC20160064","article-title":"The role played by drug efflux pumps in bacterial multidrug resistance","volume":"61","author":"Chitsaz","year":"2017","journal-title":"Essays Biochem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2503","DOI":"10.1093\/emboj\/19.11.2503","article-title":"The homodimeric ATP-binding cassette transporter LmrA mediates multidrug transport by an alternating two-site (two-cylinder engine) mechanism","volume":"19","author":"Veen","year":"2000","journal-title":"EMBO J."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"10668","DOI":"10.1073\/pnas.93.20.10668","article-title":"Multidrug resistance mediated by a bacterial homolog of the human multidrug transporter MDR1","volume":"93","author":"Veen","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"191","DOI":"10.4103\/2141-9248.105671","article-title":"Efflux pump-mediated resistance in chemotherapy","volume":"2","author":"Ughachukwu","year":"2012","journal-title":"Ann. Med. Health Sci. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"35193","DOI":"10.1074\/jbc.M306226200","article-title":"The ATP binding cassette multidrug transporter LmrA and lipid transporter MsbA have overlapping substrate specificities","volume":"278","author":"Reuter","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1038\/s41586-018-0083-5","article-title":"Structural basis for dual-mode inhibition of the ABC transporter MsbA","volume":"557","author":"Ho","year":"2018","journal-title":"Nature"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"4865","DOI":"10.1128\/JB.00756-13","article-title":"MacA, a periplasmic membrane fusion protein of the macrolide transporter MacAB-TolC, binds lipopolysaccharide core specifically and with high affinity","volume":"195","author":"Lu","year":"2013","journal-title":"J. Bacteriol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1178636119889629","DOI":"10.1177\/1178636119889629","article-title":"Identification of AcrAB-TolC Efflux Pump Genes and Detection of Mutation in Efflux Repressor AcrR from Omeprazole Responsive Multidrug-Resistant Escherichia coli Isolates Causing Urinary Tract Infections","volume":"12","author":"Chowdhury","year":"2019","journal-title":"Microbiol. Insights"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Chetri, S., Bhowmik, D., Paul, D., Pandey, P., Chanda, D.D., Chakravarty, A., Bora, D., and Bhattacharjee, A. (2019). AcrAB-TolC efflux pump system plays a role in carbapenem non-susceptibility in Escherichia coli. BMC Microbiol., 19.","DOI":"10.1186\/s12866-019-1589-1"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3472","DOI":"10.1016\/j.jmb.2019.04.002","article-title":"beta-Lactamases and beta-Lactamase Inhibitors in the 21st Century","volume":"431","author":"Tooke","year":"2019","journal-title":"J. Mol. Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1007\/s00431-020-03714-4","article-title":"Swiss consensus recommendations on urinary tract infections in children","volume":"180","author":"Buettcher","year":"2021","journal-title":"Eur. J. Pediatr."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2175","DOI":"10.3389\/fmicb.2019.02175","article-title":"Characterization of Beta-Lactamases in Bloodstream-Infection Escherichia coli: Dissemination of blaADC\u2013162 and blaCMY-2 Among Bacteria via an IncF Plasmid","volume":"10","author":"Xiao","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Gatya Al-Mayahie, S.M., Al-Guranie, D.R.T., Hussein, A.A., and Bachai, Z.A. (2022). Prevalence of common carbapenemase genes and multidrug resistance among uropathogenic Escherichia coli phylogroup B2 isolates from outpatients in Wasit Province\/Iraq. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0262984"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"248","DOI":"10.51620\/0869-2084-2021-66-4-248-256","article-title":"Epidemiological characteristics of uropatogenic iso-lates of Escherichia coli in hospitals","volume":"66","author":"Kuznetsova","year":"2021","journal-title":"Russ. Clin. Lab. Diagn."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e00821-19","DOI":"10.1128\/mSystems.00821-19","article-title":"Coexistence of Antibiotic Resistance Genes and Virulence Factors Deciphered by Large-Scale Complete Genome Analysis","volume":"5","author":"Pan","year":"2020","journal-title":"mSystems"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1111\/mmi.14235","article-title":"The plasmid-borne quinolone resistance protein QnrB, a novel DnaA-binding protein, increases the bacterial mutation rate by triggering DNA replication stress","volume":"111","author":"Li","year":"2019","journal-title":"Mol. Microbiol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3387","DOI":"10.1128\/AAC.45.12.3387-3392.2001","article-title":"Intrinsic resistance of Mycobacterium smegmatis to fluoroquinolones may be influenced by new pentapeptide protein MfpA","volume":"45","author":"Montero","year":"2001","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1587","DOI":"10.1128\/JB.01205-08","article-title":"The pentapeptide repeat proteins MfpAMt and QnrB4 exhibit opposite effects on DNA gyrase catalytic reactions and on the ternary gyrase-DNA-quinolone complex","volume":"191","author":"Merens","year":"2009","journal-title":"J. Bacteriol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.1128\/AAC.02167-15","article-title":"Mutations That Enhance the Ciprofloxacin Resistance of Escherichia coli with qnrA1","volume":"60","author":"Vinue","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1016\/j.tim.2014.04.007","article-title":"Fluoroquinolone resistance: Mechanisms, impact on bacteria, and role in evolutionary success","volume":"22","author":"Redgrave","year":"2014","journal-title":"Trends Microbiol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1128\/microbiolspec.VMBF-0016-2015","article-title":"Mechanisms of Antibiotic Resistance","volume":"4","author":"Munita","year":"2016","journal-title":"Microbiol. Spectr."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1016\/j.cell.2007.03.004","article-title":"Molecular mechanisms of antibacterial multidrug resistance","volume":"128","author":"Alekshun","year":"2007","journal-title":"Cell"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"326","DOI":"10.21037\/atm.2016.09.14","article-title":"Resistance mechanisms","volume":"4","author":"Cag","year":"2016","journal-title":"Ann. Transl. Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2042","DOI":"10.3389\/fmicb.2016.02042","article-title":"Multidrug- and Extensively Drug-Resistant Uropathogenic Escherichia coli Clinical Strains: Phylogenetic Groups Widely Associated with Integrons Maintain High Genetic Diversity","volume":"7","author":"Ochoa","year":"2016","journal-title":"Front. Microbiol."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Bonnin, R.A., Poirel, L., Carattoli, A., and Nordmann, P. (2012). Characterization of an IncFII plasmid encoding NDM-1 from Escherichia coli ST131. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0034752"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"e2498","DOI":"10.1073\/pnas.1601208113","article-title":"Antibiotic treatment enhances the genome-wide mutation rate of target cells","volume":"113","author":"Long","year":"2016","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1016\/j.bbapap.2008.11.005","article-title":"Outer membrane permeability and antibiotic resistance","volume":"1794","author":"Delcour","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"e00088-17","DOI":"10.1128\/CMR.00088-17","article-title":"Mobile Genetic Elements Associated with Antimicrobial Resistance","volume":"31","author":"Partridge","year":"2018","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1007\/s00284-005-0501-4","article-title":"High prevalence of multidrug resistance and random distribution of mobile genetic elements among uropathogenic Escherichia coli (UPEC) of the four major phylogenetic groups","volume":"53","author":"Rijavec","year":"2006","journal-title":"Curr. Microbiol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.1101\/gr.2289704","article-title":"Mauve: Multiple alignment of conserved genomic sequence with rearrangements","volume":"14","author":"Darling","year":"2004","journal-title":"Genome Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1007\/978-1-4939-0554-6_12","article-title":"Identification of mutations in laboratory-evolved microbes from next-generation sequencing data using breseq","volume":"1151","author":"Deatherage","year":"2014","journal-title":"Methods Mol. Biol."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Barrick, J.E., Colburn, G., Deatherage, D.E., Traverse, C.C., Strand, M.D., Borges, J.J., Knoester, D.B., Reba, A., and Meyer, A.G. (2014). Identifying structural variation in haploid microbial genomes from short-read resequencing data using breseq. BMC Genom., 15.","DOI":"10.1186\/1471-2164-15-1039"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.chom.2019.10.022","article-title":"A Bioinformatic Analysis of Integrative Mobile Genetic Elements Highlights Their Role in Bacterial Adaptation","volume":"27","author":"Durrant","year":"2020","journal-title":"Cell Host Microbe"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"20130838","DOI":"10.1098\/rsbl.2013.0838","article-title":"Rates of transposition in Escherichia coli","volume":"9","author":"Sousa","year":"2013","journal-title":"Biol. Lett."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/0168-9525(89)90039-5","article-title":"Eukaryotic transposable elements and genome evolution","volume":"5","author":"Finnegan","year":"1989","journal-title":"Trends Genetics"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1002\/jobm.201800204","article-title":"Transposons: The agents of antibiotic resistance in bacteria","volume":"58","author":"Babakhani","year":"2018","journal-title":"J. Basic Microbiol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"549254","DOI":"10.3389\/fmicb.2020.549254","article-title":"Genomic Characterization of Multidrug-Resistant Escherichia coli BH100 Sub-strains","volume":"11","author":"Carvalho","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1128\/MMBR.63.3.507-522.1999","article-title":"Transposon Tn21, flagship of the floating genome","volume":"63","author":"Liebert","year":"1999","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1128\/microbiolspec.MDNA3-0060-2014","article-title":"The Tn3-family of Replicative Transposons","volume":"3","author":"Nicolas","year":"2015","journal-title":"Microbiol. Spectr."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1016\/0092-8674(79)90228-9","article-title":"DNA sequence analysis of the transposon Tn3: Three genes and three sites involved in transposition of Tn3","volume":"18","author":"Heffron","year":"1979","journal-title":"Cell"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"e00452-20","DOI":"10.1128\/mBio.00452-20","article-title":"Toxin-Antitoxin Gene Pairs Found in Tn3 Family Transposons Appear To Be an Integral Part of the Transposition Module","volume":"11","author":"Ross","year":"2020","journal-title":"mBio"},{"key":"ref_85","first-page":"3212","article-title":"Multidrug Resistant Uropathogenic Escherichia coli ST405 With a Novel, Composite IS26 Transposon in a Unique Chromosomal Location","volume":"9","author":"McKinnon","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s13100-021-00239-x","article-title":"The IS6 family, a clinically important group of insertion sequences including IS26","volume":"12","author":"Varani","year":"2021","journal-title":"Mob. DNA"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"e0064621","DOI":"10.1128\/mSystems.00646-21","article-title":"IS26 Is Responsible for the Evolution and Transmission of blaNDM-Harboring Plasmids in Escherichia coli of Poultry Origin in China","volume":"6","author":"Zhao","year":"2021","journal-title":"mSystems"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.nmni.2018.10.004","article-title":"Draft genome sequence of a uropathogenic Escherichia coli isolate (ST38 O1:H15) from Pakistan, an emerging multidrug-resistant sequence type with a high virulence profile","volume":"27","author":"Rafaque","year":"2019","journal-title":"New Microbes New Infect."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.jgar.2018.10.001","article-title":"Draft genome sequence of a multidrug-resistant CTX-M-15 beta-lactamase-producing uropathogenic Escherichia coli isolate (ST131-O25b-H30) from Pakistan exhibiting high potential virulence","volume":"15","author":"Rafaque","year":"2018","journal-title":"J. Glob. Antimicrob. Resist."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.1093\/jac\/dkz117","article-title":"Characterization of the stability and dynamics of Tn6330 in an Escherichia coli strain by nanopore long reads","volume":"74","author":"Li","year":"2019","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.ijantimicag.2017.10.004","article-title":"Integrons in Enterobacteriaceae: Diversity, distribution and epidemiology","volume":"51","author":"Kaushik","year":"2018","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.envint.2018.04.041","article-title":"Critical knowledge gaps and research needs related to the environmental dimensions of antibiotic resistance","volume":"117","author":"Larsson","year":"2018","journal-title":"Environ. Int."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"6699","DOI":"10.1128\/JB.183.22.6699-6706.2001","article-title":"Integron integrases possess a unique additional domain necessary for activity","volume":"183","author":"Messier","year":"2001","journal-title":"J. Bacteriol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2472","DOI":"10.3389\/fmicb.2019.02472","article-title":"Complex Class 1 Integron in a Clinical Escherichia coli Strain From Vietnam Carrying Both mcr-1 and bla NDM-1","volume":"10","author":"Tran","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"335","DOI":"10.15171\/apb.2015.047","article-title":"Carriage of Class 1 and 2 Integrons in Quinolone, Extended-Spectrum-beta-Lactamase-Producing and Multi Drug Resistant, E.coli and K.pneumoniae: High Burden of Antibiotic Resistance","volume":"5","author":"Shams","year":"2015","journal-title":"Adv. Pharm. Bull."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.micpath.2018.02.006","article-title":"Horizontal transfer of class 1 integrons from uropathogenic Escherichia coli to E. coli K12","volume":"117","author":"Poey","year":"2018","journal-title":"Microb. Pathog."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.micpath.2014.11.002","article-title":"Integrons in uropathogenic Escherichia coli and their relationship with phylogeny and virulence","volume":"77","author":"Poey","year":"2014","journal-title":"Microb. Pathog."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1099\/jmm.0.000468","article-title":"Occurrence and characterization of class 1 integrons in Escherichia coli from healthy individuals and those with urinary infection","volume":"66","author":"Diamantino","year":"2017","journal-title":"J. Med. Microbiol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"105348","DOI":"10.1016\/j.micpath.2021.105348","article-title":"Identification and characterization of class 1 integrons among multidrug-resistant uropathogenic Escherichia coli strains in Mexico","volume":"162","author":"Balcazar","year":"2022","journal-title":"Microb. Pathog."},{"key":"ref_100","first-page":"282","article-title":"Frequency of Antimicrobial Resistance and Class 1 and 2 Integrons in Escherichia coli Strains Isolated from Urinary Tract Infections","volume":"19","author":"Mirnezami","year":"2020","journal-title":"Iran. J. Pharm. Res."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"103593","DOI":"10.1016\/j.micpath.2019.103593","article-title":"Uropathogenic Escherichia coli strains harboring tosA gene were associated to high virulence genes and a multidrug-resistant profile","volume":"134","author":"Ochoa","year":"2019","journal-title":"Microb. Pathog."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1093\/jac\/dkx488","article-title":"Plasmids carrying antimicrobial resistance genes in Enterobacteriaceae","volume":"73","author":"Rozwandowicz","year":"2018","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.jgar.2019.03.002","article-title":"Genotypic analysis of uropathogenic Escherichia coli to understand factors that impact the prevalence of beta-lactam-resistant urinary tract infections in a community","volume":"19","author":"Tarlton","year":"2019","journal-title":"J. Glob. Antimicrob. Resist."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"105256","DOI":"10.1016\/j.micpath.2021.105256","article-title":"Whole genome global insight of antibiotic resistance gene repertoire and virulome of high\u2013risk multidrug-resistant Uropathogenic Escherichiacoli","volume":"161","author":"Mitra","year":"2021","journal-title":"Microb. Pathog."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1089\/mdr.2020.0432","article-title":"Phenotypic and Genotypic Characteristics of Uropathogenic Escherichia coli Isolates from Kenya","volume":"28","author":"Muriuki","year":"2022","journal-title":"Microb. Drug Resist."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"2850183","DOI":"10.1155\/2020\/2850183","article-title":"Characterization of Plasmid-Mediated Quinolone Resistance and Serogroup Distributions of Uropathogenic Escherichia coli among Iranian Kidney Transplant Patients","volume":"2020","author":"Sadeghi","year":"2020","journal-title":"Biomed. Res. Int."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1186\/s13099-017-0207-8","article-title":"Existence of a novel qepA variant in quinolone resistant Escherichia coli from aquatic habitats of Bangladesh","volume":"9","author":"Rahman","year":"2017","journal-title":"Gut Pathog."},{"key":"ref_108","first-page":"8050432","article-title":"Molecular Identification of Aminoglycoside-Modifying Enzymes and Plasmid-Mediated Quinolone Resistance Genes among Klebsiella pneumoniae Clinical Isolates Recovered from Egyptian Patients","volume":"2017","author":"Tawakol","year":"2017","journal-title":"Int. J. Microbiol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1080\/20477724.2018.1547542","article-title":"Multiple antibiotic resistances and virulence markers of uropathogenic Escherichia coli from Mexico","volume":"112","author":"Bautista","year":"2018","journal-title":"Pathog. Glob. Health"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.jgar.2018.03.009","article-title":"Incidence and risk of co-transmission of plasmid-mediated quinolone resistance and extended-spectrum beta-lactamase genes in fluoroquinolone-resistant uropathogenic Escherichia coli: A first study from Kolkata, India","volume":"14","author":"Basu","year":"2018","journal-title":"J. Glob. Antimicrob. Resist."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"2334","DOI":"10.3389\/fmicb.2017.02334","article-title":"Clonal Diversity, Virulence Potential and Antimicrobial Resistance of Escherichia coli Causing Community Acquired Urinary Tract Infection in Switzerland","volume":"8","author":"Baschera","year":"2017","journal-title":"Front. Microbiol."},{"key":"ref_112","first-page":"277","article-title":"The antibiotic resistance crisis: Part 1: Causes and threats","volume":"40","author":"Ventola","year":"2015","journal-title":"Pharm. Ther."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"146","DOI":"10.12688\/wellcomeopenres.16847.1","article-title":"There is no market for new antibiotics: This allows an open approach to research and development","volume":"6","author":"Klug","year":"2021","journal-title":"Wellcome Open Res."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"e66481","DOI":"10.7554\/eLife.66481","article-title":"Dynamic persistence of UPEC intracellular bacterial communities in a human bladder-chip model of urinary tract infection","volume":"10","author":"Sharma","year":"2021","journal-title":"Elife"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"ftz022","DOI":"10.1093\/femspd\/ftz022","article-title":"Fosfomycin tromethamine activity on biofilm and intracellular bacterial communities produced by uropathogenic Escherichia coli isolated from patients with urinary tract infection","volume":"77","author":"Gonzalez","year":"2019","journal-title":"Pathog. Dis."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1855","DOI":"10.1128\/AAC.00014-10","article-title":"Persistence of uropathogenic Escherichia coli in the face of multiple antibiotics","volume":"54","author":"Blango","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1126\/scitranslmed.3003021","article-title":"Treatment and prevention of urinary tract infection with orally active FimH inhibitors","volume":"3","author":"Cusumano","year":"2011","journal-title":"Sci. Transl. Med."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/s41429-021-00477-4","article-title":"Combination of bactericidal antibiotics and inhibitors of Universal stress protein A (UspA): A potential therapeutic alternative against multidrug resistant Escherichia coli in urinary tract infections","volume":"75","author":"Bandyopadhyay","year":"2022","journal-title":"J. Antibiot."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1002\/em.22267","article-title":"The SOS system: A complex and tightly regulated response to DNA damage","volume":"60","author":"Maslowska","year":"2019","journal-title":"Environ. Mol. Mutagen."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"222","DOI":"10.4161\/viru.2.3.16143","article-title":"Urinary tract infection drives genome instability in uropathogenic Escherichia coli and necessitates translesion synthesis DNA polymerase IV for virulence","volume":"2","author":"Gawel","year":"2011","journal-title":"Virulence"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1016\/j.csbj.2021.01.003","article-title":"Targeting evolution of antibiotic resistance by SOS response inhibition","volume":"19","author":"Yakimov","year":"2021","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"e0001321","DOI":"10.1128\/AAC.00013-21","article-title":"Role of the SOS Response in the Generation of Antibiotic Resistance In Vivo","volume":"65","author":"Crane","year":"2021","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1080\/21505594.2019.1596507","article-title":"Ciprofloxacin, amoxicillin, and aminoglycosides stimulate genetic and phenotypic changes in uropathogenic Escherichia coli strains","volume":"10","author":"Wawszczak","year":"2019","journal-title":"Virulence"},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Hocquet, D., Llanes, C., Thouverez, M., Kulasekara, H.D., Bertrand, X., Plesiat, P., Mazel, D., and Miller, S.I. (2012). Evidence for induction of integron-based antibiotic resistance by the SOS response in a clinical setting. PLoS Pathog., 8.","DOI":"10.1371\/journal.ppat.1002778"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"118562","DOI":"10.1016\/j.lfs.2020.118562","article-title":"The central role of the SOS DNA repair system in antibiotics resistance: A new target for a new infectious treatment strategy","volume":"262","author":"Memar","year":"2020","journal-title":"Life Sci."},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Bunnell, B.E., Escobar, J.F., Bair, K.L., Sutton, M.D., and Crane, J.K. (2017). Zinc blocks SOS-induced antibiotic resistance via inhibition of RecA in Escherichia coli. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0178303"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"2188","DOI":"10.1093\/jac\/dkz210","article-title":"N-acetylcysteine blocks SOS induction and mutagenesis produced by fluoroquinolones in Escherichia coli","volume":"74","author":"Valencia","year":"2019","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"e00971-17","DOI":"10.1128\/mBio.00971-17","article-title":"Quinolone Resistance Reversion by Targeting the SOS Response","volume":"8","author":"Recacha","year":"2017","journal-title":"mBio"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/8\/1397\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:05:04Z","timestamp":1760141104000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/8\/1397"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,6]]},"references-count":128,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2022,8]]}},"alternative-id":["genes13081397"],"URL":"https:\/\/doi.org\/10.3390\/genes13081397","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,6]]}}}