Ingenious strategies of microbial pathogens

Silencing innate immunity During infection, microbes traverse or invade a variety of biological niches in which they are challenged by the innate immune responses of host cells. Katherine Owen (Casanova lab, University of Virginia, Charlottesville) showed that intracellular Salmonella escape autophagosomal degradation by activating mTOR through the FAK/ Akt kinase pathway. This process requires pathogenicity island 2 (SPI-2), a key virulence system in Salmonella. Interference with SPI-2 function or depletion of host cell FAK renders Salmonella less capable of evading autophagosomal degradation, protecting mice from otherwise lethal Salmonella infections. Matthias Machner (National Institutes of Health) described how Legionella pneumophila bypasses endolysosomal degradation. Legionella produces VipD, a phospholipase A1 that specifically localizes to early endosomes by binding to the host cell GTPase Rab5. The phospholipase activity of VipD alters the lipid and, consequently, protein composition of endosomal membranes, rendering them fusion-incompetent and protecting Legionella from degradation. Andrew Woolery (Orth lab, UT Southwestern) demonstrated that the Vibrio parahaemolyticus protein VopS covalently modifies host cell Rho GTPases with AMP not only to disable the actin cytoskeleton but also to inhibit downstream signaling through several host immune pathways, including NFκB, MAP kinase, the inhibitor of apoptosis proteins (IAP), and the phagocytic NADPH oxidase system (NOX2). All three talks illustrated the critical role of interference with innate immune mechanisms in survival of bacterial pathogens.