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This content will become publicly available on April 8, 2026

Title: Structural basis of aggregative adherence fimbriae II interactions with sialic acid, mucin, and human intestinal cells
ABSTRACT EnteroaggregativeEscherichia coli(EAEC) is a common cause of diarrhea worldwide and is associated with growth faltering in developing countries. EAEC are defined by a characteristic adherence pattern mediated by the aggregative adherence fimbriae (AAFs). Despite the critical role of AAF in the definition of the EAEC pathotype, it is not known what host molecules mediate adherence and EAEC pathogenesis during infection of the human gastrointestinal tract. Multiple receptor candidates have been proposed based onin vitroexperimentation. We propose that AAFs interact with multiple receptors during colonization of the human gastrointestinal mucosa, and we hypothesize that structural features of the AafA protein (the major subunit of AAF variant II produced by EAEC strain 042) promote these diverse interactions. In this study, we utilize a panel of AafA variants encoding single amino acid substitutions to understand the role of individual residues in biofilm formation as well as adherence to mucin, fibronectin, and human intestinal cells. We identify both charged and uncharged residues that participate in these interactions, and these residues cluster in two regions of the protein that may define a binding pocket at the junction of polymerized subunits. Although both bovine submaxillary mucin and human fibronectin are sialylated molecules, adherence to mucin is diminished by the removal of sialic acid residues while adherence to fibronectin is not, suggesting that the mechanisms of adherence to these molecules are distinct. Overall, our data provide insight into the structural features that determine AAF/II binding to mucin, sialic acid, and human intestinal cells.  more » « less
Award ID(s):
2024182
PAR ID:
10623693
Author(s) / Creator(s):
; ; ; ;
Editor(s):
Raffatellu, Manuela
Publisher / Repository:
ASM journals
Date Published:
Journal Name:
Infection and Immunity
Volume:
93
Issue:
4
ISSN:
0019-9567
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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