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

Citation
Lim J, Stones DH, Hawley CA, Watson CA & Krachler AM (2014) Multivalent Adhesion Molecule 7 Clusters Act as Signaling Platform for Host Cellular GTPase Activation and Facilitate Epithelial Barrier Dysfunction, PLoS Pathogens, 10 (9), Art. No.: e1004421.

Abstract
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. © 2014 Lim et al.

StatusPublished
AuthorsLim Jenson, Stones Daniel H, Hawley Catherine Alice, Watson Charlie Anne, Krachler Anne Marie
Publication date25/09/2014
Publication date online25/09/2014
Date accepted by journal25/08/2014
PublisherPublic Library of Science
ISSN 1553-7366
LanguageEnglish

Journal
Plos Pathogens: Volume 10, Issue 9 (2014)

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