7 May 2014, 12pm-1pm, GLT3, Warwick Medical School Building, University of Warwick
'Adhesin-induced lipid coalescence in the host membrane causes activation of a Rho GTPase and loss of epithelial barrier integrity'
Dr Anne Marie Krachler, Birmingham Fellow and EMBO Fellow, Institute of Microbiology and Infection, School of Biosciences, University of Birmingham
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 host cells. More recently, we found that the bacterial adhesin, through multivalent, high-affinity interactions with phosphatidic acids, induces lipid coalescence in the host cell membrane. Clustering of lipid ligands triggers downstream activation of the small GTPase RhoA and actin rearrangements in host cells. In infection studies with V. parahaemolyticus we further demonstrate that adhesin-triggered RhoA activation is sufficient to disrupt tight junctions, leading to a loss of epithelial barrier function. Taken together, these findings show a previously unrecognized mechanism by which an adhesin acts as an assembly platform for a membrane lipid at the host-pathogen synapse, causing downstream signalling processes which ultimately facilitate transepithelial migration of a bacterial pathogen.
Anne-Marie Krachler joined the University of Birmingham as a Birmingham Fellow and EMBO Fellow in 2012 and is based at the Institute of Microbiology and Infection within the School of Biosciences. Her lab studies interactions between bacterial pathogens and their host and how this knowledge can be used to fight bacterial infections and gain novel insight into eukaryotic signalling mechanisms.