Multifactorial resistance mechanisms associated with tigecycline resistance in Escherichia coli
- سال انتشار: 1402
- محل انتشار: بیست و چهارمین کنگره بین المللی میکروب شناسی ایران
- کد COI اختصاصی: MEDISM24_069
- زبان مقاله: انگلیسی
- تعداد مشاهده: 78
نویسندگان
Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran
چکیده
BACKGROUND AND OBJECTIVESTigecycline (TGC) is one of the last-resort antimicrobial agents for the treatment of serious infections caused by extensively drug-resistant Enterobacteriaceae. TGC resistance is found to be mainly mediated by overexpression of RND-type efflux pumps (AcrAB), mutations in ribosomal S۱۰ protein (rpsJ) or plasmid-encoded Tet(A) and acquisition of plasmid-encoded tetX family genes.MATERIALS AND METHODSSeven TGC resistant Escherichia coli mutants (MICs= ۲ to ۸ mg/L) were obtained by exposing three different TGC susceptible isolates (MIC= ۰.۲۵ mg/L) to increasing concentrations of TGC. Whole genome sequencing was performed to identify genetic alterations associated with reduced susceptibility to TGC. The fitness cost of TGC resistance acquisition was investigated by comparing the in vitro growth rate of TGC resistant mutants to that of their wild-type ancestors in an antibiotic-free medium.RESULTS AND DISCUSSIONThe majority of studied mutants were found to carry genetic alterations in regulators of AcrAB efflux pump. More genetic alterations were also identified in other loci such as those coding for lipopolysaccharide core biosynthesis enzymes as well as ribosomal protein. In most cases but not all, the growth rate of mutants in an antibiotic-free environment was lower than those of wild-type parent isolates indicating presence of fitness cost for TGC resistance acquisition.CONCLUSIONThe molecular mechanisms involved in TGC resistance among the studied isolates was found to be very diverse, with increased extrusion of antibiotic by efflux pumps being found as the major mechanism.کلیدواژه ها
Tigecycline resistance, Escherichia coli, efflux pump, ribosomal proteinمقالات مرتبط جدید
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