Microbiology Select

This edition of Select highlights recent papers that explore some of the ever-evolving strategies that are used by microbes to subvert eukaryotic immune systems, and by host cells to fight off bacterial and viral pathogens. A number of intracellular pathogens, including Shigella flexneri, the causative agent of dysentery, co-opt the cytoskeletal elements of their host cells. These bacterial pathogens nucleate actin tails at one of their cell poles that enable them to propel them through the cytoplasm and invade neighboring host cells. The motility patterns of the bacterial cells vary in speed and in the number of stops and turns made in their journey. Yoshida et al. (2006) now report that Shigella's ease of movement is greatly impeded by host cell microtubules. It turns out that Shigella secretes a protease-like protein, VirA, that fragments microtubules thus clearing a path for itself and other bacteria. A Shigella mutant lacking VirA has dramatically reduced motility within infected cells despite forming normal actin tails. Treating the infected cells with noco-dazole, a microtubule-depolymerizating agent, rescues the motility defect of the mutant Shigella and enhances the speed and efficiency of the wild-type bacterium. ''Tunnels'' of cleared microtubules coincident with the path of wild-type Shigella can be visualized, and other bacteria tend to follow the lead bacterium along the same path. Higher-resolution imaging revealed microtubule fragments in the wake of the pioneering bacterium. The virA mutant Shigella could not forge ''tunnels,'' indicating that VirA was the agent of microtubule demise. Indeed, purified VirA could fragment microtubules in vitro, and further biochemical characterization revealed that VirA degrades a-tubulin via cysteine protease activity. A strain of S. flexneri bearing a mutation at VirA's catalytic cysteine displayed reduced motility and attenuated pathogenicity in a mouse model of infection. Future work will determine if other motile intracellular pathogens secrete proteins that fragment microtubules or whether they recruit host factors to do it for them. The causative agent of typhoid, Salmonella typhi, and its mouse-adapted cousin, Salmonella typhimurium, are engulfed by gut phagocytes and transported to the bloodstream where they become efficiently disseminated, launching a systemic infection. The rapidity with which these pathogens end up in the bloodstream can be some sixty times greater than the normal migration time of phagocytes journeying from the gut to the bloodstream. Now Worley et al. (2006) reveal that S. typhimurium has a weapon among its arsenal of secreted virulence factors that enables it to …