Abstract
This study profiled the prevalence of extended-spectrum ß-lactamase-producing Escherichia coli (ESBL-EC) in the community and compared their resistome and genomic profiles with isolates from clinical patients through whole-genome sequencing. Fecal samples from 233 community dwellers from Segamat, a town in southern Malaysia, were obtained between May through August 2018. Putative ESBL strains were screened and tested using antibiotic susceptibility tests. Additionally, eight clinical ESBL-EC were obtained from a hospital in the same district between June through October 2020. Whole-genome sequencing was then conducted on selected ESBL-EC from both settings (n = 40) for pan-genome comparison, cluster analysis, and resistome profiling. A mean ESBL-EC carriage rate of 17.82% (95% CI: 10.48%- 24.11%) was observed in the community and was consistent across demographic factors. Whole-genome sequences of the ESBL-EC (n = 40) enabled the detection of multiple plasmid replicon groups (n = 28), resistance genes (n = 34) and virulence factors (n = 335), with no significant difference in the number of genes carried between the community and clinical isolates (plasmid replicon groups, p = 0.13; resistance genes, p = 0.47; virulence factors, p = 0.94). Virulence gene marker analysis detected the presence of extraintestinal pathogenic E. coli (ExPEC), uropathogenic E. coli (UPEC), and enteroaggregative E. coli (EAEC) in both the community and clinical isolates. Multiple blaCTX-M variants were observed, dominated by blaCTX-M-27 (n = 12), blaCTX-M-65 (n = 10), and blaCTX-M-15 (n = 9). The clinical and community isolates did not cluster together based on the pan-genome comparison, suggesting isolates from the two settings were clonally unrelated. However, cluster analysis based on carried plasmids, resistance genes and phenotypic susceptibility profiles identified four distinct clusters, with similar patterns between the community and clinical isolates. ESBL-EC from the clinical and community settings shared similar resistome profiles, suggesting the frequent exchange of genetic materials through horizontal gene transfer.
Highlights
The Centers for Disease Control and Prevention (CDC) has classified extended-spectrum ßlactamase (ESBL) expression in Enterobacteriaceae as a serious threat to public health due to limited therapeutic options and challenges in controlling its transmission [1]
Pan-genome and resistome analysis of ESBL-producing Escherichia coli from multiple settings in Malaysia
Its rapid emergence is driven by the successful acquisition of various virulence factors associated with extraintestinal pathogenic E. coli (ExPEC), such as the iutA aerobactin receptor and papG P fimbrial adhesin virulence genes [14]
Summary
The Centers for Disease Control and Prevention (CDC) has classified extended-spectrum ßlactamase (ESBL) expression in Enterobacteriaceae as a serious threat to public health due to limited therapeutic options and challenges in controlling its transmission [1]. The surveillance of ESBL is complicated by the commensal and hardy nature of Enterobacteriaceae, where ESBL has been reported from the clinical setting and in asymptomatic community dwellers [2–4], wastewater [5, 6], farm animals and pets [7, 8], and even natural environments [9, 10]. These nonclinical settings often lack regular antibiotic surveillance and monitoring, rendering them reservoirs for ESBL and other antibiotic resistance genes which can potentially supply these resistance determinants to virulent and pathogenic strains. ESBL dissemination can be carried and disseminated by commensal strains through horizontal gene transfer of plasmids carrying the ESBL gene [18], as observed in community studies (e.g., [2, 7])
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