Evolutionary Dynamics Based on Comparative Genomics of Pathogenic Escherichia coli Lineages Harboring Polyketide Synthase ( pks ) Island

Abstract

The genotoxin colibactin is a secondary metabolite produced by the polyketide synthase (pks) island harbored by extraintestinal pathogenic E. coli (ExPEC) and other members of the Enterobacteriaceae that has been increasingly reported to have critical implications in human health. The present study entails a high-throughput whole-genome comparison and phylogenetic analysis of such pathogenic E. coli isolates to gain insights into the patterns of distribution, horizontal transmission, and evolution of the island. For the current study, 23 pks-positive ExPEC genomes were newly sequenced, and their virulome and resistome profiles indicated a preponderance of virulence encoding genes and a reduced number of genes for antimicrobial resistance. In addition, 4,090 E. coli genomes from the public domain were also analyzed for large-scale screening for pks-positive genomes, out of which a total of 530 pks-positive genomes were studied to understand the subtype-based distribution pattern(s). The pks island showed a significant association with the B2 phylogroup (82.2%) and a high prevalence in sequence type 73 (ST73; n = 179) and ST95 (n = 110) and the O6:H1 (n = 110) serotype. Maximum-likelihood (ML) phylogeny of the core genome and intergenic regions (IGRs) of the ST95 model data set, which was selected because it had both pks-positive and pks-negative genomes, displayed clustering in relation to their carriage of the pks island. Prevalence patterns of genes encoding RM systems in the pks-positive and pks-negative genomes were also analyzed to determine their potential role in pks island acquisition and the maintenance capability of the genomes. Further, the maximum-likelihood phylogeny based on the core genome and pks island sequences from 247 genomes with an intact pks island demonstrated horizontal gene transfer of the island across sequence types and serotypes, with few exceptions. This study vitally contributes to understanding of the lineages and subtypes that have a higher propensity to harbor the pks island-encoded genotoxin with possible clinical implications. IMPORTANCE Extraintestinal pathologies caused by highly virulent strains of E. coli amount to clinical implications with high morbidity and mortality rates. Pathogenic E. coli strains are evolving with the horizontal acquisition of mobile genetic elements, including pathogenicity islands such as the pks island, which produces the genotoxin colibactin, resulting in severe clinical outcomes, including colorectal cancer progression. The current study encompasses high-throughput comparative genomics and phylogenetic analyses to address the questions pertaining to the acquisition and evolution pattern of the genomic island in different E. coli subtypes. It is crucial to gain insights into the distribution, transfer, and maintenance of pathogenic islands, as they harbor multiple virulence genes involved in pathogenesis and clinical implications of the infection.

Gut Microbiota as Potential Biomarker and/or Therapeutic Target to Improve the Management of Cancer: Focus on Colibactin-Producing Escherichia coli in Colorectal Cancer

“…Notably, the pks island was identified in extraintestinal pathogenic E. coli but has also been found in other members of the family Enterobacteriaceae ( Klebsiella pneumoniae , Enterobacter aerogenes , and Citrobacter koseri ). The pks genomic island phylogeny indicated horizontal acquisition/transmission and the possibility of exchange between compatible E. coli subtypes [ 123 ].…”

Bacterial Toxins Are a Never-Ending Source of Surprises: From Natural Born Killers to Negotiators

“…The pks island is present in pathogenic, commensal, and even probiotic bacterial strains [ 24 ]. Large-scale whole-genome-based studies have investigated the pks island phylogeny and suggested the possibility of horizontal acquisition/transmission and exchange between compatible E. coli subtypes [ 42 ].…”

Genome Dynamics and Evolution of Multiple-Drug–Resistant Bacteria: Implications for Global Infection Control Priorities

“…Our previous observations demonstrated high numbers of AMR genes as a part of genomic investigations of globally distributed and epidemiologically successful sequence types (STs) of E. coli such as ST131, ST38, ST405, and ST648 [ 4 ]. In another study, we observed that E. coli isolates that carry the genotoxin encoding pks island displayed lower phenotypic AMR as well as lower prevalence of AMR genes (especially the specific AMR determinants such as target inactivation/modification genes) [ 18 ].…”