Yale Researchers Discover Infectious Mechanism Common to Many Bacteria

Scientists at Yale School of Medicine have described the means by which many common bacteria that cause potentially fatal diseases-such as food poisoning, typhoid fever, plague and dysentery-infect other cells, raising hopes for the development of new treatments for the diseases.

In a paper published in the November 1 issue of Nature, Jorge Gal‡n, the Lucille P. Markey Professor of Microbiology and chair of the Section of Microbial Pathogenesis, and C. Erec Stebbins, a post-doctoral fellow in his laboratory, report finding how the type III secretion system in Salmonella, the cause of food poisoning and typhoid fever, works to inject a host cell with bacterial protein.

“Many pathogens use a similar mechanism,” said Galan. “Insight into any of them gives you insight into all of them. From this fundamental information, we can begin to develop completely new therapeutic strategies to halt or prevent infections by these pathogens.”

According to Galan, many bacterial pathogens have evolved the type III secretion system, an organelle that has a hollow, needle-like structure to deliver bacterial proteins into the host cell to subvert its functions for the pathogen’s benefit. His research used a synchrotron particle accelerator at the Brookhaven National Laboratory in Long Island, New York, to generate ultra-high resolution images from which the structure of key components of this system were derived. The scientists found that in order to be injected into host cells by the type III secretion system, the bacterial proteins need to bind to an associated chaperone protein that allows them to retain features necessary to be recognized by the “injection organelle.”

Among the many bacterial pathogens making use of the type III secretion systems to cause disease are those in E. coli (the cause of hemolytic uremic syndrome), Yersinia pestis (the cause of plague), Shigella (the cause of dysentery) and Pseudomonas aeruginosa, which causes devastating diseases in children with cystic fibrosis. The bacteria are responsible for many thousands of disease cases and deaths in the United States and elsewhere in the world every year.

Preventing the secreted proteins from binding to an associated chaperone protein could potentially halt infectious diseases spread by the various bacteria and also may give investigators a new strategy for developing new treatments against these bacterial diseases. Galan and colleagues hope to further their studies by understanding how the chaperone protein releases the secreted protein into the host cell.

The study was supported by the Cancer Research Fund of the Damon Runyon-Walter Winchell Foundation and Public Health Services grants.

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Karen N. Peart: karen.peart@yale.edu, 203-432-1326