Pan-Genome Analysis with Virulence Factors: Charting the Genomic Landscape of Uropathogenic Escherichia coli (UPEC)

Abstract

Urinary tract infections remain a worldwide health challenge, affecting over 150 million individuals annually, with significant morbidity and healthcare costs. Escherichia coli is the chief uropathogen (50–90%) in uncomplicated, community-acquired urinary tract infections. Numerous virulence factors are expressed by Uropathogenic Escherichia coli (UPEC), allowing the bacteria to cause urinary tract infections. Despite large-scale sequencing efforts to raise clinical awareness of UPEC, not much is known about the diversity and functions of virulence factors. To understand and elucidate the genetic diversity, evolutionary characteristics, and virulence profile, efforts were taken to construct the pan-genome of UPEC using 212 publicly available complete genome sets. The UPEC pan-genome was open in nature i.e. its size increases indefinitely when adding new genomes and showed extensive genome variability. These UPEC strains had diverse virulence gene content, and four potential core virulence genes (dhak, fimH-1, H-2, uspABCDFG, yehD) have been identified. The conserved mechanisms for their pathogenicity were related to adherence, motility, and immune modulation. The study underscores the crucial role of bacterial adhesins, particularly fimH, in mediating UPEC attachment to uroepithelial cells, enhancing persistence, and resisting mechanical elimination by urine flow. The investigation into fimH single-nucleotide polymorphisms aids in understanding UPEC epidemiological types. The datasets provide in-depth analysis of genomic diversity and virulence profiles of UPEC strains, paving the way for the development of effective preventive and therapeutic strategies. Therefore, the identified virulence factors with further research can serve as potential targets for vaccine and antibiotic development, facilitating genetic studies and clinical research for enhanced UTI management.