Identification of genes subject to positive selection in uropathogenic strains of Escherichia coli : A comparative genomics approach

Abstract

Escherichia coli is a model laboratory bacterium, a species that is widely distributed in the environment, as well as a mutualist and pathogen in its human hosts. As such, E. coli represents an attractive organism to study how environment impacts microbial genome structure and function. Uropathogenic E. coli (UPEC) must adapt to life in several microbial communities in the human body, and has a complex life cycle in the bladder when it causes acute or recurrent urinary tract infection (UTI). Several studies designed to identify virulence factors have focused on genes that are uniquely represented in UPEC strains, whereas the role of genes that are common to all E. coli has received much less attention. Here we describe the complete 5,065,741-bp genome sequence of a UPEC strain recovered from a patient with an acute bladder infection and compare it with six other finished E. coli genome sequences. We searched 3,470 ortholog sets for genes that are under positive selection only in UPEC strains. Our maximum likelihood-based analysis yielded 29 genes involved in various aspects of cell surface structure, DNA metabolism, nutrient acquisition, and UTI. These results were validated by resequencing a subset of the 29 genes in a panel of 50 urinary, periurethral, and rectal E. coli isolates from patients with UTI. These studies outline a computational approach that may be broadly applicable for studying strain-specific adaptation and pathogenesis in other bacteria.uropathogenic Escherichia coli ͉ ecogenomics

An inducible lambdoid prophage encoding cytolethal distending toxin (Cdt-I) and a type III effector protein in enteropathogenic Escherichia coli

“…The genome of CDT-1⌽ reveals a highly mosaic structure with homology to sequences derived from several bacteriophages and bacterial genomes of different categories of pathogenic E. coli, as well as Shigella sonnei, S. flexneri, and S. typhimurium (SI Table 4), suggesting that the evolution of these phages and bacterial strains involved extensive horizontal exchange of genetic material. Interestingly, the genes responsible for head and tail, integrase, regulation, and lysis are highly conserved between CDT-1⌽ and a previously described putative prophage UTI89 of uropathogenic E. coli (20). However, the genomic regions corresponding to virulence and ''unknown functions'' were not conserved between CDT-1⌽ and prophage UTI89.…”

“…Interestingly, OmpC was identified as a receptor molecule for phage T4 (23), and some uropathogenic E. coli strains including a strain harboring prophage UTI89 highly expressed OmpC protein (20). It is possible that CDT-1⌽ preferably infects diverse E. coli strains, which highly express OmpC.…”

“…The genomic organization of CDT-1⌽ was found to be more similar to those of phage SfV of S. flexneri (18) and prophage UTI89 (20) of an uropathogenic E. coli strain than Stx2⌽-I (21) (Fig. 2 and SI Fig.…”

“…However, these additional bands could also have generated from other phages having homology to CDT-1 prophage and that may exist in these strains together with the CDT-1 prophage. Notably, the genomic sequence of CDT-1⌽ has homology with UTI89 prophage (20) and the prophage-like element of EPEC strain B171 ( Fig. 2 and SI Table 4), although these latter phages do not have the virulence regions containing the cdt gene cluster.…”

“…This observation suggested that the OmpC protein might play a crucial role in the infection of E. coli by CDT-1⌽. Given that OmpC was identified as a receptor for phage T4 (23), and that certain uropathogenic E. coli strains including a strain UPI89 harboring a prophage UTI89 hyperexpressed OmpC protein (20), it is likely that OmpC also acts as a receptor for CDT-1⌽. However, further studies will be required to confirm this assumption.…”