The rhs genes are a family of composite genes widespread throughout Gram-negative bacteria, but the functions of the molecules they encode remain largely unknown. In the Proceedings of the National Academy of Sciences, Hauser and colleagues attribute an inflammasome-activation role to RhsT from Pseudomonas aeruginosa. RhsT is expressed at the bacterial cell surface and is translocated into macrophages during coculture. That translocation results in the death (pyroptosis) of macrophages and is accompanied by more release of IL-1b and IL-18. Transfection of RhsT alone is sufficient to induce pyroptosis. Inhibition of caspase-1 or knockout of ASC demonstrates that pyroptosis and the release of inflammatory cytokines in response to RhsT requires assembly and/or activation of the inflammasome. Finally, in a mouse model of acute pneumonia, the authors observe that an isogenic mutant of RhsT induces less inflammation and is much less toxic to hosts. RhsT is thus an important virulence factor for P. aeruginosa that acts via inflammasome activation.

Proc. Natl. Acad. Sci. USA 109, 1275–1280 (2012)