Dataset Information

Genome analysis of E. coli isolated from Crohn's disease patients.

ABSTRACT: BACKGROUND:Escherichia coli (E. coli) has been increasingly implicated in the pathogenesis of Crohn's disease (CD). The phylogeny of E. coli isolated from Crohn's disease patients (CDEC) was controversial, and while genotyping results suggested heterogeneity, the sequenced strains of E. coli from CD patients were closely related. RESULTS:We performed the shotgun genome sequencing of 28 E. coli isolates from ten CD patients and compared genomes from these isolates with already published genomes of CD strains and other pathogenic and non-pathogenic strains. CDEC was shown to belong to A, B1, B2 and D phylogenetic groups. The plasmid and several operons from the reference CD-associated E. coli strain LF82 were demonstrated to be more often present in CDEC genomes belonging to different phylogenetic groups than in genomes of commensal strains. The operons include carbon-source induced invasion GimA island, prophage I, iron uptake operons I and II, capsular assembly pathogenetic island IV and propanediol and galactitol utilization operons. CONCLUSIONS:Our findings suggest that CDEC are phylogenetically diverse. However, some strains isolated from independent sources possess highly similar chromosome or plasmids. Though no CD-specific genes or functional domains were present in all CD-associated strains, some genes and operons are more often found in the genomes of CDEC than in commensal E. coli. They are principally linked to gut colonization and utilization of propanediol and other sugar alcohols.

SUBMITTER: Rakitina DV

PROVIDER: S-EPMC5517970 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Genome analysis of E. coli isolated from Crohn's disease patients.

Rakitina Daria V DV Manolov Alexander I AI Kanygina Alexandra V AV Garushyants Sofya K SK Baikova Julia P JP Alexeev Dmitry G DG Ladygina Valentina G VG Kostryukova Elena S ES Larin Andrei K AK Semashko Tatiana A TA Karpova Irina Y IY Babenko Vladislav V VV Ismagilova Ruzilya K RK Malanin Sergei Y SY Gelfand Mikhail S MS Ilina Elena N EN Gorodnichev Roman B RB Lisitsyna Eugenia S ES Aleshkin Gennady I GI Scherbakov Petr L PL Khalif Igor L IL Shapina Marina V MV Maev Igor V IV Andreev Dmitry N DN Govorun Vadim M VM

BMC genomics 20170719 1

<h4>Background</h4>Escherichia coli (E. coli) has been increasingly implicated in the pathogenesis of Crohn's disease (CD). The phylogeny of E. coli isolated from Crohn's disease patients (CDEC) was controversial, and while genotyping results suggested heterogeneity, the sequenced strains of E. coli from CD patients were closely related.<h4>Results</h4>We performed the shotgun genome sequencing of 28 E. coli isolates from ten CD patients and compared genomes from these isolates with already publ ...[more]

PMID: 28724357

Similar Datasets

Project description:Crohn's disease (CD) is a complex and highly heterogeneous chronic inflammatory disorder, primarily affecting the gastrointestinal tract. Genetic and functional studies have highlighted a key role for innate immunity in its pathogenesis. Profound systemic defects in innate immunity and acute inflammation are understood to result in markedly delayed clearance of bacteria from the tissues, leading to local chronic granulomatous inflammation and compensatory adaptive immunological changes. Macrophages, key orchestrators of acute inflammation, are likely to play an important role in the initial impaired innate immune response. Monocyte-derived macrophages from CD patients stimulated with E. coli were shown to release attenuated levels of TNF and IFNM-NM-3 with normal secretion of IL8, IL10 and IL6. In controls, the secretion of these cytokines was strongly positively correlated, which was not seen with CD macrophages. The transcriptomes of CD and control macrophages were examined in an attempt to understand the molecular basis of this defect. There were no differentially expressed genes identified between the two groups, consistent with genetic heterogeneity; however, a number of molecules were found to be under-expressed in subgroups of CD patients. The most common of these was optineurin (OPTN) which was under-expressed in approximately 10% of the CD patients. Reduced OPTN expression coincided with lower intracellular protein levels and diminished cytokine secretion after bacterial stimulation both in the patients and with siRNA knockdown in THP-1 cells. Identifying and studying subgroups of patients with shared defective gene expression could aid our understanding of the mechanisms underlying highly heterogeneous diseases such as CD. Total RNA obtained from monocyte derived macrophages from Crohn's disease patients (n=58) or healthy volenteers (n=42) were cultured for six days before being stimulated with heat killed E. coli for four hours or left unstimulated.

Dataset Information

Genome analysis of E. coli isolated from Crohn's disease patients.

Publications

Genome analysis of E. coli isolated from Crohn's disease patients.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets