The Escherichia coli species represents one of the best-studied model organisms, but also encompasses a variety of commensal and pathogenic strains that diversify by high rates of genetic change. We uniformly (re-) annotated the genomes of 20 commensal and pathogenic E. coli strains and one strain of E. fergusonii (the closest E. coli related species), including seven that we sequenced to completion. Within the ∼18,000 families of orthologous genes, we found ∼2,000 common to all strains. Although recombination rates are much higher than mutation rates, we show, both theoretically and using phylogenetic inference, that this does not obscure the phylogenetic signal, which places the B2 phylogenetic group and one group D strain at the basal position. Based on this phylogeny, we inferred past evolutionary events of gain and loss of genes, identifying functional classes under opposite selection pressures. We found an important adaptive role for metabolism diversification within group B2 and Shigella strains, but identified few or no extraintestinal virulence-specific genes, which could render difficult the development of a vaccine against extraintestinal infections. Genome flux in E. coli is confined to a small number of conserved positions in the chromosome, which most often are not associated with integrases or tRNA genes. Core genes flanking some of these regions show higher rates of recombination, suggesting that a gene, once acquired by a strain, spreads within the species by homologous recombination at the flanking genes. Finally, the genome's long-scale structure of recombination indicates lower recombination rates, but not higher mutation rates, at the terminus of replication. The ensuing effect of background selection and biased gene conversion may thus explain why this region is A+T-rich and shows high sequence divergence but low sequence polymorphism. Overall, despite a very high gene flow, genes co-exist in an organised genome.

We previously suggested that the ability to metabolize deoxyribose, a phenotype encoded by the deoK operon, is associated with the pathogenic potential of Escherichia coli strains. Carbohydrate metabolism is thought to provide the nutritional support required for E. coli to colonize the intestine. We therefore investigated the role of deoxyribose catabolism in the colonization of the gut, which acts as a reservoir, by pathogenic E. coli strains. Molecular and biochemical characterization of 1,221 E. coli clones from various collections showed this biochemical trait to be common in the E. coli species (33.6%). However, multivariate analysis evidenced a higher prevalence of sugar-metabolizing E. coli clones in the stools of patients from countries in which intestinal diseases are endemic. Diarrhea processes frequently involve the destruction of intestinal epithelia, so it is plausible that such clones may be positively selected for in intestines containing abundant DNA, and consequently deoxyribose. Statistical analysis also indicated that symptomatic clinical disorders and the presence of virulence factors specific to extraintestinal pathogenic E. coli were significantly associated with an increased risk of biological samples and clones testing positive for deoxyribose. Using the streptomycintreated-mouse model of intestinal colonization, we demonstrated the involvement of the deoK operon in gut colonization by two pathogenic isolates (one enteroaggregative and one uropathogenic strain). These results, indicating that deoxyribose availability promotes pathogenic E. coli growth during host colonization, suggest that the acquisition of this trait may be an evolutionary step enabling these pathogens to colonize and persist in the mammalian intestine.Escherichia coli is a normal inhabitant of the intestines of healthy individuals. However, under certain circumstances, E. coli can also be a serious pathogen in humans and animals. Many studies over the last 30 years have focused on the identification and description of numerous virulence factors and the genes encoding them. There is now a substantial body of knowledge concerning the development of three major clinical syndromes caused by these bacteria: urinary tract infections (UTI), sepsis/meningitis, and diarrhea. The strains causing the extraintestinal diseases are referred to as ExPEC (extraintestinal pathogenic E. coli) strains and include uropathogenic E. coli and sepsis/meningitis-associated E. coli strains. The intestinal pathogens are distributed into at least six well-described pathovars-enteropathogenic E. coli, Shiga toxin-producing E. coli, enterotoxigenic E. coli, enteroinvasive E. coli, enteroaggregative E. coli (EAEC), and diffusely adherent E. coliwhich exhibit differing physiopathological behavior patterns (33, 41). The reservoir for all pathogenic E. coli strains is the gut, and it remains unclear how pathogenic E. coli strains outcompete the gut microflora to colonize the mammalian intestine and how they survive in this complex ecosystem. Increasin...

e Uropathogenic Escherichia coli (UPEC) strains are a leading cause of infections in humans, but the mechanisms governing host colonization by this bacterium remain poorly understood. Previous studies have identified numerous gene clusters encoding proteins involved in sugar transport, in pathogen-specific islands. We investigated the role in fitness and virulence of the vpe operon encoding an EII complex of the phosphotransferase (PTS) system, which is found more frequently in human strains from infected urine and blood (45%) than in E. coli isolated from healthy humans (15%). We studied the role of this locus in vivo, using the UPEC E. coli strain AL511, mutants, and complemented derivatives in two experimental mouse models of infection. Mutant strains displayed attenuated virulence in a mouse model of sepsis. A role in kidney colonization was also demonstrated by coinfection experiments in a mouse model of pyelonephritis. Electron microscopy examinations showed that the vpeBC mutant produced much smaller amounts of a capsule-like surface material than the wild type, particularly when growing in human urine. Complementation of the vpeBC mutation led to an increase in the amount of exopolysaccharide, resistance to serum killing, and virulence. It was therefore clear that the loss of vpe genes was responsible for all the observed phenotypes. We also demonstrated the involvement of the vpe locus in gut colonization in the streptomycin-treated mouse model of intestinal colonization. These findings confirm that carbohydrate transport and metabolism underlie the ability of UPEC strains to colonize the host intestine and to infect various host sites. E scherichia coli is a normal resident bacterium of the intestines of healthy humans. However, in certain circumstances, it may also cause serious disease in humans. Uropathogenic E. coli (UPEC) strains are facultative pathogens that are present as commensal organisms in the normal flora of some healthy people. They are responsible for 80 to 90% of urinary tract infections (UTI) in humans (3,17,53). Many UTI are asymptomatic, but some UPEC strains cause significant clinical symptoms, ranging from pain in uncomplicated cases of cystitis to sepsis in cases of pyelonephritis. Antibiotic treatment may be difficult if the strains concerned are multiresistant (27). Despite tremendous advances in our understanding of the genetic bases of pathogenicity and of the evolutionary diversity of UPEC strains over the last 10 years (28), the mechanisms by which UPEC strains colonize the human intestine, which serves as their reservoir, and then travel to and persist in the urinary tract (UT) remain poorly understood. These bacteria frequently express adhesin/invasin and toxin genes and are equipped with iron acquisition systems and mechanisms for evading the immune response, through the production of extracellular polysaccharides, for example. However, no virulence factor or set of factors has yet been identified as essential for gut colonization and infection of the bladder or kidney. ...