School of Chemistry and Molecular Biosciences, The University of Queenslandgrid.1003.2, Brisbane, Queensland, Australia.
Australian Infectious Diseases Research Centre, The University of Queenslandgrid.1003.2, Brisbane, Queensland, Australia.
Antimicrob Agents Chemother. 2022 Jan 18;66(1):e0214621. doi: 10.1128/AAC.02146-21. Epub 2021 Nov 15.
Escherichia coli ST131 is a recently emerged antibiotic resistant clone responsible for high rates of urinary tract and bloodstream infections. Despite its global dominance, the precise mechanisms that have driven the rapid dissemination of ST131 remain unknown. Here, we show that the plasmid-associated resistance gene encoding the AAC(6')-Ib-cr enzyme that inactivates the fluoroquinolone (FQ) antibiotic ciprofloxacin is present in >70% of strains from the most rapidly expanding subgroup of multidrug resistant ST131. Using a series of genome-edited and plasmid-cured isogenic strains, we demonstrate that the gene confers a selective advantage on ST131 in the presence of ciprofloxacin, even in strains containing chromosomal GyrA and ParC FQ-resistance mutations. Further, we identify a pattern of emerging carbapenem resistance in other common E. coli clones carrying both and chromosomal FQ-resistance mutations, suggesting this dual resistance combination may also impart a selective advantage on these non-ST131 antibiotic resistant lineages.
大肠杆菌 ST131 是一种新近出现的抗生素耐药克隆，可导致尿路感染和血流感染的高发病率。尽管它在全球占据主导地位，但推动 ST131 快速传播的确切机制仍不清楚。在这里，我们表明，携带编码使氟喹诺酮（FQ）抗生素环丙沙星失活的 AAC(6')-Ib-cr 酶的质粒相关耐药基因存在于耐药性 ST131 中快速扩张的亚群的>70%的菌株中。通过一系列基因组编辑和质粒消除的同基因株，我们证明即使在含有染色体 GyrA 和 ParC FQ 耐药突变的菌株中， 基因在环丙沙星存在下也赋予 ST131 选择性优势。此外，我们在携带 和染色体 FQ 耐药突变的其他常见大肠杆菌克隆中发现了一种新兴碳青霉烯耐药模式，表明这种双重耐药组合也可能赋予这些非 ST131 抗生素耐药谱系选择性优势。
