Insights into enterotoxigenic Escherichia coli diversity in Bangladesh utilizing genomic epidemiology

Enterotoxigenic Escherichia coli (ETEC) cause more than 500,000 deaths each year in the developing world and are characterized on a molecular level by the presence of genes that encode the heat-stable (ST) and/or heat-labile (LT) enterotoxins, as well as surface structures, known as colonization factors (CFS). Genome sequencing and comparative genomic analyses of 94 previously uncharacterized ETEC isolates demonstrated remarkable genomic diversity, with 28 distinct sequence types identified in three phylogenomic groups. Interestingly, there is a correlation between the genomic sequence type and virulence factor profiles based on prevalence of the isolate, suggesting that there is an optimal combination of genetic factors required for survival, virulence and transmission in the most successful clones. A large-scale BLAST score ratio (LS-BSR) analysis was further applied to identify ETEC-specific genomic regions when compared to non-ETEC genomes, as well as genes that are more associated with clinical presentations or other genotypic markers. Of the strains examined, 21 of 94 ETEC isolates lacked any previously identified CF. Homology searches with the structural subunits of known CFS identified 6 new putative CF variants. These studies provide a roadmap to exploit genomic analyses by directing investigations of pathogenesis, virulence regulation and vaccine development.