Abstract
Enteroaggregative Escherichia coli (EAEC) is an emerging cause of acute and persistent diarrhea worldwide. The pathogenesis of different EAEC stains is complicated, however, the early essential step begins with attachment of EAEC to intestinal mucosa via aggregative adherence fimbriae (AAFs). Currently, five different variants have been identified, which all share a degree of similarity in the gene organization of their operons and sequences. Here, we report the solution structure of Agg5A from the AAF/V variant. While preserving the major structural features shared by all AAF members, only Agg5A possesses an inserted helix at the beginning of the donor strand, which together with altered surface electrostatics, renders the protein unable to interact with fibronectin. Hence, here we characterize the first AAF variant with a binding mode that varies from previously described AAFs
Highlights
Enteroaggregative Escherichia coli (EAEC) is a subgroup of diarrheagenic E. coli, which is recognized as a major cause of diarrhea worldwide
The adherence of EAEC to the human intestinal mucosa requires expression of aggregative adherence fimbriae (AAFs), where adherence is characterized as a biofilm composed by aggregates of bacteria in association with a thick mucus layer [12,13]
We report nuclear magnetic resonance (NMR) studies of the monomeric, donor-strand complemented major pilin subunit of Agg5A, the newest member of the AAF family, which was recently shown to be very prevalent among EAEC strains isolated from Danish travelers with diarrhea (12%) and from children in Mali with diarrhea (13%) [18]
Summary
Enteroaggregative Escherichia coli (EAEC) is a subgroup of diarrheagenic E. coli, which is recognized as a major cause of diarrhea worldwide. Studies have previously shown that the archetype EAEC strain 042 expressing AAF/II binds to several major extra cellular matrix (ECM) proteins present in the intestinal epithelium, such as fibronectin, laminin, and type IV collagen [24]. From these data as well as validation by NMR and surface plasmon resonance (SPR), it was suggested that the AAFs have evolved an electrostatic mechanism for binding to host cell receptors using a patch of positively charged residues [22]. Our results show that Agg5A displays significantly differences from AafA and AggA, suggesting an evolutionary adaption to an alternative host receptor
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: Biochimica et biophysica acta. Proteins and proteomics
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
