Genome sequence of adherent-invasive Escherichia coli and comparative genomic analysis with other E. coli pathotypes - PubMed (original) (raw)

Comparative Study

Genome sequence of adherent-invasive Escherichia coli and comparative genomic analysis with other E. coli pathotypes

John He Nash et al. BMC Genomics. 2010.

Abstract

Background: Adherent and invasive Escherichia coli (AIEC) are commonly found in ileal lesions of Crohn's Disease (CD) patients, where they adhere to intestinal epithelial cells and invade into and survive in epithelial cells and macrophages, thereby gaining access to a typically restricted host niche. Colonization leads to strong inflammatory responses in the gut suggesting that AIEC could play a role in CD immunopathology. Despite extensive investigation, the genetic determinants accounting for the AIEC phenotype remain poorly defined. To address this, we present the complete genome sequence of an AIEC, revealing the genetic blueprint for this disease-associated E. coli pathotype.

Results: We sequenced the complete genome of E. coli NRG857c (O83:H1), a clinical isolate of AIEC from the ileum of a Crohn's Disease patient. Our sequence data confirmed a phylogenetic linkage between AIEC and extraintestinal pathogenic E. coli causing urinary tract infections and neonatal meningitis. The comparison of the NRG857c AIEC genome with other pathogenic and commensal E. coli allowed for the identification of unique genetic features of the AIEC pathotype, including 41 genomic islands, and unique genes that are found only in strains exhibiting the adherent and invasive phenotype.

Conclusions: Up to now, the virulence-like features associated with AIEC are detectable only phenotypically. AIEC genome sequence data will facilitate the identification of genetic determinants implicated in invasion and intracellular growth, as well as enable functional genomic studies of AIEC gene expression during health and disease.

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Figures

Figure 1

Figure 1

Comparative genome atlas of NRG857c. The chromosome of NRG857c (two outermost rings are CDS on forward and reverse strand) was compared with those of selected E. coli strains, starting from the outer layer LF82 (AIEC; pale green), APEC-O1 (APEC; blue), CFT073 (UPEC; yellow), MG1655 (K12/commensal; purple) and enterohemorrhagic E. coli O157:H7 Sakai (EHEC, red). Genomic islands were plotted on the NRG857c chromosome (grey blocks). The G+C content and G/C skew are also plotted as indicated.

Figure 2

Figure 2

Phylogenetic analysis of NRG857c compared with representative strains of other enteric bacteria. (A) A phylogenetic tree based on the unweighted pair group method with arithmetic mean was constructed from the optimal map data and in silico Nco_I_ restriction digests of other enteric bacterial chromosomes. (B) MLST-based analysis of NRG857c with other enteric bacteria was performed as described in the Methods and sequence data was used to construct a phylogenetic tree. Numbers on the tree branches represent bootstrap support from 1000 bootstrap replicates with a minimum cut-off of 65%. Accession numbers for gene sequences can be found in Additional File 2, Table S1.

Figure 3

Figure 3

Genomic islands in NRG857c. Genomic islands in the NRG857c chromosome (A) and plasmid (B) were predicted using stringent bioinformatics criteria as described in the Methods. Genomic islands are plotted to scale in blue and labelled clockwise on the genome maps. On the plasmid, genes involved in antimicrobial resistance are indicated in red.

Figure 4

Figure 4

Gene content analysis of plasmid pNRG857c and comparison to representative strains of other E. coli. BLASTN analysis was performed between each CDS in plasmid pNRG857c against each CDS in pLF82, pO157Sakai, pUTI89, and pAPEC-O1-ColBM. Genes in pNRG857c with orthologs in the other plasmids, defined as >85% identity over entire length of the gene, are connected with a coloured line.

Figure 5

Figure 5

Iron uptake by the aerobactin system is important for intracellular survival and for mouse colonization. (A) J774.A1 macrophage cells were infected with wild type NRG857c or iutA mutant cells. The survival of intracellular bacteria was determined at various times after infection. Data are the mean survival of intracellular bacteria with standard deviation. (*, P < 0.05, Mann Whitney) (B) The aerobactin iron transport system improves colonization in vivo. Groups of mice were infected orally with wild type NRG857c or iutA mutants. Colonization of the small intestine by NRG857c AIEC was determined three days after infection by enumerating the number of cfu in tissue homogenates. Data are the means with standard errors. (**, P < 0.005, Mann Whitney).

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