Commensal Fitness Advantage May Contribute to the Global Dissemination of Multidrug-Resistant Lineages of Bacteria—The Case of Uropathogenic E. coli

Abstract

It is widely accepted that favorable fitness in commensal colonization is one of the prime facilitators of clonal dissemination in bacteria. The question arises as to what kind of fitness advantage may be wielded by uropathogenic strains of the two predominant fluoroquinolone- and multidrug-resistant clonal groups of E. coli—ST131-H30 and ST1193, which has permitted their unprecedented pandemic-like global expansion in the last few decades. The colonization-associated genes’ content, carriage of low-cost plasmids, and integrons with weak promoters could certainly contribute to the fitness of the pandemic groups, although those genetic factors are common among other clonal groups as well. Also, ST131-H30 and ST1193 strains harbor fluoroquinolone-resistance conferring mutations targeting serine residues in DNA gyrase (GyrA-S83) and topoisomerase IV (ParC-S80) that, in those clonal backgrounds, might result in a commensal fitness benefit, i.e., beyond the antibiotic resistance per se. This fitness gain might have contributed not only to the widespread dissemination of these major clones in the healthcare setting but also to their long-term colonization of healthy individuals and, thus, circulation in the community, even in a low or no fluoroquinolone use environment. This evolutionary shift affecting commensal E. coli, initiated by mutations co-favorable in both antibiotics-treated patients and healthy individuals warrants more in-depth studies to monitor further changes in the epidemiological situation and develop effective measures to reduce the antibiotic resistance spread.

Quantifying the genomic determinants of fitness inE. coliST131 using phylodynamics

“…Virulence factors that enhance fitness seem to be those that allow ST131 to colonize and persist, like cnf /α -hly, cvaC , and fdeC , rather than those that increase disease severity. These results are consistent with recent hypotheses that the main environment in which ST131 thrives, evolves, and transmits is the gut of individuals in the community, not necessarily in antibiotic-rich hospital settings [9, 20, 59, 60]. Pitout and Finn [61] further suggest that this unique virulence profile may allow these lineages to persist in, and move between, different hosts and environments where they have more opportunity to be exposed to, and subsequently acquire, a diverse range of plasmids and other mobile genetic elements that allow them to rapidly adapt to new environments and outcompete the resident microbial population [62].…”

Gut residentEscherichia coliprofile predicts the eighteen-month probability and antimicrobial susceptibility of urinary tract infections

“…Though our study did not analyze the duration of gut colonization per se, it suggests that uropathogenic antibiotic-resistant strains can reside in the gut for a relatively long time, making the 18-month predictability of the urinary pathogen feasible. This corresponds to previous studies suggesting that E. coli H30 and ST1193 strains may be well-adapted as colonizers [12, 34, 35, 61].…”

“…ST1193 emerged later than E. coli H30 but started to challenge the latter in global UTI predominance in the mid-late 2010s [29, 31]. It has been proposed that the phenomenal global spread of both E. coli H30 and ST1193 is associated with their success as gut colonizers, possibly connected to the mutations responsible for CIP resistance [35, 36]. The fact that E. coli H30 is significantly more commonly carried by older women corresponds to our previous findings in a smaller prior study [11].…”

Fluoroquinolone resistance in complicated urinary tract infections: association with the increased occurrence and diversity of Escherichia coli of clonal complex 131, together with ST1193

“…Therefore, the substantial reduction in the prescription of FQ in the recent decade is not significantly generating a decrease in the percentage of FQR or decrease in the circulation of these MDR clones ( Tchesnokova et al., 2023 ). In addition to the energetically favorable QRDR mutations, the carriage of low-cost plasmids and integrons with weak promoters and some virulence factors (colonization-associated genes) may have also a fitness-favorable impact in these clones ( Fuzi and Sokurenko, 2023 ). On the other hand, the need of an appropriate genetic background exposed by the selective epistasis hypothesis would explain why other E. coli strains with the same set of QRDR mutation could not achieve the same level of notoriety ( Cummins et al., 2021 ; Fuzi and Sokurenko, 2023 ).…”

“…In addition to the energetically favorable QRDR mutations, the carriage of low-cost plasmids and integrons with weak promoters and some virulence factors (colonization-associated genes) may have also a fitness-favorable impact in these clones ( Fuzi and Sokurenko, 2023 ). On the other hand, the need of an appropriate genetic background exposed by the selective epistasis hypothesis would explain why other E. coli strains with the same set of QRDR mutation could not achieve the same level of notoriety ( Cummins et al., 2021 ; Fuzi and Sokurenko, 2023 ). In this context, the spread of highly successful clones that manifest an adaptative advantage with respect to other clones, and with capacity of colonization, currently represents a serious sanitary issue despite a reduction in antibiotic pressure.…”