Comparative genomics of Escherichia coli isolated from patients with inflammatory bowel disease

<p>Abstract</p> <p>Background</p> <p>Inflammatory bowel disease (IBD) is used to describe a state of idiopathic, chronic inflammation of the gastrointestinal tract. The two main phenotypes of IBD are Crohn's disease (CD) and ulcerative colitis (UC). The major cause of IBD-associated mortality is colorectal cancer. Although both host-genetic and exogenous factors have been found to be involved, the aetiology of IBD is still not well understood. In this study we characterized thirteen <it>Escherichia coli </it>strains from patients with IBD by comparative genomic hybridization employing a microarray based on 31 sequenced <it>E. coli </it>genomes from a wide range of commensal and pathogenic isolates.</p> <p>Results</p> <p>The IBD isolates, obtained from patients with UC and CD, displayed remarkably heterogeneous genomic profiles with little or no evidence of group-specific determinants. No IBD-specific genes were evident when compared with the prototypic CD isolate, LF82, suggesting that the IBD-inducing effect of the strains is multifactorial. Several of the IBD isolates carried a number of extraintestinal pathogenic <it>E. coli </it>(ExPEC)-related virulence determinants such as the <it>pap</it>, <it>sfa</it>, <it>cdt </it>and <it>hly </it>genes. The isolates were also found to carry genes of ExPEC-associated genomic islands.</p> <p>Conclusions</p> <p>Combined, these data suggest that <it>E. coli </it>isolates obtained from UC and CD patients represents a heterogeneous population of strains, with genomic profiles that are indistinguishable to those of ExPEC isolates. Our findings indicate that IBD-induction from <it>E. coli </it>strains is multifactorial and that a range of gene products may be involved in triggering the disease.</p

A Novel Protein Kinase-Like Domain in a Selenoprotein, Widespread in the Tree of Life

Selenoproteins serve important functions in many organisms, usually providing essential oxidoreductase enzymatic activity, often for defense against toxic xenobiotic substances. Most eukaryotic genomes possess a small number of these proteins, usually not more than 20. Selenoproteins belong to various structural classes, often related to oxidoreductase function, yet a few of them are completely uncharacterised

A broad range quorum sensing inhibitor working through sRNA inhibition

For the last decade, chemical control of bacterial virulence has received considerable attention. Ajoene, a sulfur-rich molecule from garlic has been shown to reduce expression of key quorum sensing regulated virulence factors in the opportunistic pathogen Pseudomonas aeruginosa. Here we show that the repressing effect of ajoene on quorum sensing occurs by inhibition of small regulatory RNAs (sRNA) in P. aeruginosa as well as in Staphylococcus aureus, another important human pathogen that employs quorum sensing to control virulence gene expression. Using various reporter constructs, we found that ajoene lowered expression of the sRNAs RsmY and RsmZ in P. aeruginosa and the small dual-function regulatory RNA, RNAIII in S. aureus, that controls expression of key virulence factors. We confirmed the modulation of RNAIII by RNA sequencing and found that the expression of many QS regulated genes encoding virulence factors such as hemolysins and proteases were lowered in the presence of ajoene in S. aureus. Importantly, our findings show that sRNAs across bacterial species potentially may qualify as targets of anti-virulence therapy and that ajoene could be a lead structure in search of broad-spectrum compounds transcending the Gram negative-positive borderline

A virulent parent with probiotic progeny: comparative genomics of Escherichia coli strains CFT073, Nissle 1917 and ABU 83972

Escherichia coli is a highly versatile species encompassing a diverse spectrum of strains, i.e. from highly virulent isolates causing serious infectious diseases to commensals and probiotic strains. Although much is known about bacterial pathogenicity in E. coli, the understanding of which genetic determinants differentiates a virulent from an avirulent strain still remains limited. In this study we designed a new comparative genomic hybridization microarray based on 31 sequenced E. coli strains and used it to compare two E. coli strains used as prophylactic agents (i.e. Nissle 1917 and 83972) with the highly virulent uropathogen CFT073. Only relatively minor genetic variations were found between the isolates, suggesting that the three strains may have originated from the same virulent ancestral parent. Interestingly, Nissle 1917 (a gut commensal strain) was more similar to CFT073 with respect to genotype and phenotype than 83972 (an asymptomatic bacteriuria strain). The study indicates that genetic variations (e.g. mutations) and expression differences, rather than genomic content per se, contribute to the divergence in disease-causing ability between these strains. This has implications for the use of virulence factors in epidemiological research, and emphasizes the need for more comparative genomic studies of closely related strains to compare their virulence potential