VirA disrupts microtubules (green) and causes membrane ruffling.

杨柳

Many invasive bacteria let themselves into host cells, not bothering to wait for an invitation. So far, known effector proteins that allow bacteria to enter work by rearranging actin dynamics. But new research from Sei Yoshida, Chihiro Sasakawa (University of Tokyo, Tokyo), and colleagues reveals that Shigella bacteria have another trick up their proverbial sleeves. They destabilize microtubules (MTs) to promote their own phagocytosis./ {8 Q, E8 v" m! ~- p( D* D
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Shigella uses the Type III secretion system to deliver a set of its effector proteins into cells it plans to invade. Some of these proteins act in well-known ways to modulate the actin cytoskeleton. For instance, IpaA binds the focal adhesion protein vinculin, and this complex promotes actin depolymerization. But the group focused on VirA, which acts independently of other effectors. Shigella lacking VirA are 70–80% less invasive than wild-type bacteria.7 d& |; c/ e" _* N8 g: f

' \3 z8 j$ G2 x' n! T6 ZThe authors found that VirA bound /?-tubulin heterodimers and destabilized MTs in vitro and in vivo. Destabilization led to membrane ruffling around the bacterium, an effect that was dependent on the activation of Rac1. Sasakawa is not yet sure how VirA binding causes MT instability. Bound heterodimers may be held less stably in the MT lattice, or VirA might compete with MTs for binding to tubulin heterodimers. VirA homologues exist in other bacteria, including E. coli, indicating that a wide range of pathogens may alter MT dynamics to aid in their invasion.2 S* q% q. ]1 f( Q% }: p& U
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Reference:
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Yoshida, S., et al. 2002. EMBO J. 21:2923–2935.(Sasakawa/EMBO)