PubMed · 15040253
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Louisa Flintoft. 2004. Pathogenic E. coli--getting intimate.. https://doi.org/10.1038/nrmicro831
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Enteropathogenic Escherichia coli (EPEC) causes disease in children, presenting as chronic diarrhea that can impair physical and cognitive development. The attachment of typical EPEC (tEPEC) to the gut epithelium via bundle-forming pili (BFP) is a key factor in its virulence. Yet, infections by atypical EPEC (aEPEC), which lack BFP, have become increasingly common. To investigate how aEPEC recover host-attachment in the absence of BFP, we performed experimental evolution using a non-adherent E. coli, constructed to mimic the ancestor of aEPEC, and selected adherent progeny. Highly adherent variants evolved through phase-variable activation of type I fimbriae (T1F), followed by two alternative trajectories: bacterial filamentation, which increases T1F avidity, or point mutations in the T1F adhesin FimH that enhance ligand affinity. Extending our analysis to the genomes of 327 aEPEC strains isolated from infected patients revealed that similar FimH mutations are common. We further demonstrated experimentally that these naturally occurring variants often increase epithelial-attachment. Our findings implicate T1F in aEPEC pathogenesis and suggest it may be clinically relevant for anti-adhesion therapy. More broadly, these results indicate that impaired host-attachment can be rapidly compensated by upregulating and optimizing an alternative adhesin, and that combining experimental evolution with comparative genomics can reveal evolutionary trajectories occurring in nature.
Bacteria frequently colonize host and environmental surfaces under fluid flow. Chain-like adherence pattern (CLAP) is an EibG-mediated surface colonization phenotype of certain Shiga toxin-producing Escherichia coli (STEC) that lack the locus of enterocyte effacement (LEE). EibG, an immunoglobulin-binding trimeric autotransporter adhesin, drives CLAP, but the temporal dynamics and genetic diversity underlying chain formation remain unclear. Here, we use live-cell time-lapse imaging to show that chains arise from single cells that elongate and divide without separation. Under flow, chains resist detachment and undergo shear-dependent fragmentation at cell-cell junctions, releasing viable clonal units that disperse downstream. Comparative genomics reveals diversity among EibG-related adhesins and identifies distinct lineages, including chain-like adhesins (Cla) that mediate CLAP while lacking IgG binding. Screening of 1,354 genomes from England shows that claB is present in 95.6% of strains from major LEE-negative STEC serotypes, highlighting its epidemiological prevalence. Targeted mutagenesis demonstrates that chain formation and IgG binding are mediated by distinct structural domains, revealing the modular functional architecture of these adhesins. Furthermore, we show that EibG, ClaA, and ClaB confer robust resistance to complement-mediated killing. Collectively, these findings establish CLAP as a dynamic, surface-associated strategy of LEE-negative STEC and reveal diversification among adhesins that drive this behavior.
The aim of the present study was to study different strains of bifidobacteria for adhesion to Caco-2 intestinal epithelial cells (IECs) and to test for the mRNA response of these cells following interaction with bifidobacteria. Adhesion was tested at different pH conditions using model epithelia consisting of transwell cultures of fully differentiated Caco-2 cells. Microarrays were used to characterize changes in global expression profiles of Caco-2 cells co-cultured with peripheral blood mononuclear cells (PBMCs) and challenged with non-pathogenic Escherichia coli D2241 or four different strains of bifidobacteria. Furthermore, cytokine mRNA of IECs in responses to challenge with Bifidobacterium bifidum S17 or E. coli D2241 was tested in PBMC-sensitised Caco-2 cells using RT-PCR. Bifidobacteria showed strain-specific adhesion to Caco-2. Shift of apical pH from 7 to 4.5 resulted in strain-specific changes of adhesion. Global expression profiles of PBMC-sensitised Caco-2 cells revealed differential expression of a significant number of genes only after challenge with E. coli D2241 while cells were essentially unresponsive to challenge with four strains of bifidobacteria showing different adhesion properties. Using a RT-PCR approach, in the same system a similar differential expression after challenge with E. coli D2241 or B. bifidum S17 was observed for various immune markers. The presented results suggest that Caco-2 cells might be specifically unresponsive to challenge with bifidobacteria irrespective of the level of adhesion.