New Insights Into the Virulence of Plague
The Yersinia species of bacteria includes agents that cause plague (Y. pestis) and gastroenteritis (Y. pseudotuberculosis and Y. enterocolitica) in humans. These three agents share a common virulence protein—Yersinia protein kinase A, or YpkA—that binds to a specific target protein in human hosts and determines the severity of infection.
A recent study by NIAID grantees for the first time shows a process by which YpkA defeats natural immune defenses and allows infection. Importantly, the work has provided scientists who work on plague with new information about how Y. pestis intoxicates human cells, and how they might prevent infection.
Led by C. Erec Stebbins, Ph.D., of Rockefeller University, in collaboration with scientists at Stony Brook University at Stony Brook, N.Y., the research team used Y. pseudotuberculosis to study the crystal structure of a previously unexamined domain within YpkA. They discovered that the structure of YpkA mimics that of a specific host protein to which the target of YpkA normally binds, limiting the target host protein’s function.
Specifically, YpkA weakens the infrastructure of the host cell and prevents desired protective shape changes. YpkA also biochemically triggers host immune defenses to shut down, allowing the invading bacteria to infect and spread throughout the host. This same mechanism should be conserved in Y. pestis and Y. enterocolitica, the researchers note.
When YpkA was modified in Y. pseudotuberculosis to prevent it from interacting with its protein target, and the modified protein was studied in mice, Stebbins’ group observed that the agent was not nearly as virulent.
Reference
Prehna, G. et al. Yersinia virulence depends on mimicry of host Rho-family nucleotide dissociation inhibitors. Cell DOI: 10.1016/j.cell.2006.06.056 (2006).
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