Genomic features of three major diarrhoeagenic Escherichia coli pathotypes in India

Background. Diarrhoea remains a major threat to children in developing nations, with diarrhoeagenic Escherichia coli (DEC) being the primary causative agent. Characterizing prevalent DEC strains is crucial, yet comprehensive genomic analyses of major DEC strains, including enteropathogenic E. coli (EPEC), enteroaggregative E. coli (EAEC) and enterotoxigenic E. coli (ETEC), are lacking in India.Methods. We sequenced 24 EAEC and 23 EPEC strains from Indian patients with diarrhoea and conducted an extensive database search for DEC human isolates from India. Detailed phylogenetic analyses, virulence gene subtyping and examinations of accessory virulence and antimicrobial resistance (AMR) genes were performed.Results. The analysed DEC strains included 32 EAEC, 25 EPEC, 32 ETEC and 1 each of the EPEC/ETEC-hybrid and ETEC/EAEC-hybrid pathotypes. These strains were predominantly classified into phylogroups A (35.2%) and B1 (41.8%) and dispersed within these phylogroups without pathotype-specific clustering. One ETEC strain was classified into cryptic clade 1. Subtypes of hallmark virulence genes varied substantially amongst strains in each pathotype, and 31 accessory virulence genes were detected either specifically within certain pathotypes or across multiple pathotypes at varying frequencies, indicating diversification of the virulence gene repertoire within each pathotype. Acquired AMR genes were found in 73.6% of the strains, with frequent identification of AMR genes for aminoglycosides (40.0%), β-lactams (64.8%), sulphonamides (49.5%) and trimethoprim (42.9%). Known quinolone-resistant mutations were found in 74.7% of the strains, whereas AMR genes for macrolide (30.8%), phenicol (11.0%) and tetracycline (27.4%) were less frequent.Conclusions. The diverse virulence potential and trends in AMR gene prevalence amongst major DEC strains in India are highlighted in this study. Continuous monitoring of DEC strain characteristics is essential for the effective control and treatment of DEC infections in India.