Abstract
The Escherichia coli ST131 H30-Rx subclone vehicles CTX-M-15 plasmids and mutations in gyrA and parC conferring multidrug resistance successfully in the clinical setting. The aim of this study was (1) to investigate the relationship of specific topoisomerase mutations on the stability of IncF (CTX-M producing) plasmids using isogenic E. coli mutants and (2) to investigate the impact of the IncF-type plasmids present in the E. coli clone ST131 on the evolution of quinolone resistance. E. coli ATCC 25922 (background strain) and derived mutants encoding specific QRDR substitutions were used. Also, NGS-characterized IncFIA and IncFIB plasmids (encoding CTX-M genes) were included. Plasmid stability was evaluated by sequential dilutions into Luria broth medium without antibiotics for 7days. Mutant frequency to ciprofloxacin was also evaluated. Moderate differences in the IncF plasmids stability were observed among E. coli ATCC 25922 and isogenic mutants. Under our experimental conditions, the fluctuation of bacteria harboring plasmids was less than 0.5-log(10) in all cases. In the mutant frequency tests, it was observed that the presence of these IncF plasmids increased this value significantly (10-1000-fold). Quinolone resistance substitutions in gyrA or parC genes, frequently found associated with E. coli clone ST131, do not modify the stability of ST131-associated IncFIA and IncFIB plasmids under in vitro conditions. IncF-type plasmids present in E. coli clone ST131 facilitate the selection of resistance to quinolones. These results are consistent with the clinical scenario in which the combination of resistance to quinolones and beta-lactams is highly frequent in the E. coli clone ST131.
Highlights
Extra-intestinal pathogenic E. coli (ExPEC) is a major human pathogen, the most common cause of urinary tract infections and the most common gram-negative bacterium associated with bloodstream infections in both developed and developing countries [1]
Next-generation sequencing (NGS) identified two sub-clades within clade C named C1/H30R and C2/H30-Rx, both sub-clades with extensive global distribution [3]
The main objective of this study was to investigate the relationship and the impact of different topoisomerase mutations frequently found related to FQ-R in E. coli ST131 clone on the stability of IncF plasmids and, on the other hand, the impact of IncF plasmids acquisition on topoisomerase modifications emergence using isogenic E. coli mutants
Summary
Extra-intestinal pathogenic E. coli (ExPEC) is a major human pathogen, the most common cause of urinary tract infections and the most common gram-negative bacterium associated with bloodstream infections in both developed and developing countries [1]. A single clone which belongs to the O25b-B2 subgroup, ST131 clone, is predominantly responsible for this global multidrug-resistant (MDR) ExPEC pandemic [2]. European Journal of Clinical Microbiology & Infectious Diseases but since the 2000s, clade C became the most dominant lineage (currently up to 80% of global ST131 belongs to clade C) [2]. Next-generation sequencing (NGS) identified two sub-clades within clade C named C1/H30R (associated with FQ-R) and C2/H30-Rx (associated with the ESBL CTX-M15), both sub-clades with extensive global distribution [3]. Substitutions such as S83L, D87N, and D87G into GyrA and S80R, S80I, and E84V into ParC have been frequently associated with FQ-R in C1/H30R and C2/H30-Rx subclades. Phylogenetic studies have shed some light regarding the origin and evolution of ST131 clade C [4, 5], showing that clade C evolved from clade B during the mid-late 1980s
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