How plague bacterium Yersinia pestis damages eukaryotic cells
As I described in this week’s podcast, Plague: From the 14th to the 21st century and still going strong, Yersinia pestis has been a major human pathogen for many centuries, and with climate change, looks set to get even worse. Part of the problem is that we still don’t have a really good understanding of how this bacterium causes disease. A paper just published in the journal Cell goes a long way towards changing that.
A critical virulence determinant in Yersinia species is the Yersinia protein kinase A, YpkA, a multidomain protein which disrupts the actin cytoskeleton in eukaryotic cells, essentially the glue which holds cells together. Despite its known importance to virulence, little has been forthcoming in understanding the mechanism of activity of YpkA. The new paper shows that YpkA possesses a Rac1 binding domain which mimics host guanidine nucleotide dissociation inhibitors (GDIs) of the Rho GTPases, so virulence in Yersinia species depends upon mimicry of host GDI proteins by YpkA. The new data strongly suggests that YpkA mimics host GDI proteins by acting as an “off switch” to modulate the Rac1-associated signaling pathways that regulate host cytoskeletal structure.
The authors also point out that it is becoming increasingly clear that mimicry of eukaryotic biochemical processes is a common strategy used by many bacterial pathogens to modulate host cell biology, something that might previously only have been ascribed to viruses.
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