Most dangerous bacteria that enter the body are engulfed and digested by cells called macrophages. Once inside a macrophage, the bacteria are targeted for death by a mechanism that transports them within a vesicle to a specialized compartment, the lysozome, designed to degrade foreign or unwanted materials.
Once the bacterium is engulfed, it takes only about 30 minutes to reach a lysozome. Therefore, to survive and replicate, bacteria must act rapidly to avoid this pathway to degradation. Salmonella, the bacterium that causes food poisoning and typhoid fever, can do that.
"Salmonella have an elegant strategy for surviving and replicating and avoiding this cellular disposal system," said Galan, the Lucille P. Markey Professor of Microbiology, and Chairman of the Section of Microbial Pathogenesis. "We found that these bacteria alter the lipid composition of the vacuole, or compartment, they are in so that it cannot progress down the standard path to the lysozome and destruction."
To accomplish this remarkable feat, the Salmonella bacteria use a "syringe-like" device called the type III secretion system to deliver a protein, SopB, which has phosphoinositide phosphatase activity and modifies the composition of the vacuole that encloses them.
"While this research is not a cure for food poisoning or typhoid fever, our work is revealing a fundamental mechanism by which these bacteria cause disease - and may provide or lead to new targets for the development of novel therapeutic strategies for controlling them," said Galan.
Other investigators involved in the study were Lorraine Hernandez and Karsten Hueffer from the Section of Microbial Pathogenesis and Markus Wenk, currently at Merck Research Laboratories, from the Department of Cell Biology at Yale. The work was funded by a fellowship from the Damon Runyon-Walter Winchell Foundation and by a Public Health Service Grant from the National Institutes of Health.
Citation: Science 304: (June 18, 2004)
Journal
Science