Multivalent Adhesion Molecule 7 Clusters Act as Signaling Platform for Host Cellular GTPase Activation and Facilitate Epithelial Barrier Dysfunction

Lim, Jenson, Stones, Daniel H ORCID: 0000-0002-8981-7943, Hawley, Catherine Alice, Watson, Charlie Anne and Krachler, Anne Marie (2014) Multivalent Adhesion Molecule 7 Clusters Act as Signaling Platform for Host Cellular GTPase Activation and Facilitate Epithelial Barrier Dysfunction. PLoS Pathogens, 10 (9). e1004421. doi:10.1371/journal.ppat.1004421

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Vibrio parahaemolyticus is an emerging bacterial pathogen which colonizes the gastrointestinal tract and can cause severe enteritis and bacteraemia. During infection, V. parahaemolyticus primarily attaches to the small intestine, where it causes extensive tissue damage and compromises epithelial barrier integrity. We have previously described that Multivalent Adhesion Molecule (MAM) 7 contributes to initial attachment of V. parahaemolyticus to epithelial cells. Here we show that the bacterial adhesin, through multivalent interactions between surface-induced adhesin clusters and phosphatidic acid lipids in the host cell membrane, induces activation of the small GTPase RhoA and actin rearrangements in host cells. In infection studies with V. parahaemolyticus we further demonstrate that adhesin-triggered activation of the ROCK/LIMK signaling axis is sufficient to redistribute tight junction proteins, leading to a loss of epithelial barrier function. Taken together, these findings show an unprecedented mechanism by which an adhesin acts as assembly platform for a host cellular signaling pathway, which ultimately facilitates breaching of the epithelial barrier by a bacterial pathogen.

Item Type: Article
Article Type: Article
Uncontrolled Keywords: Actins; Host cells; Cell binding; Cell membranes; Adhesins; Guanosine triphosphatase; Bacterial pathogens; Tight junctions; REF2021
Subjects: Q Science > QR Microbiology
Divisions: Schools and Research Institutes > School of Natural & Social Sciences > Environmental Sciences
Research Priority Areas: Place, Environment and Community
Depositing User: Daniel Stones
Date Deposited: 09 Oct 2018 08:47
Last Modified: 02 Aug 2021 05:15

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