SALMONELLA INFECTS CELLS AND SAVES ITSELF BY ALTERING HOST MEMBRANE LIPIDS
18 June 2004 - Yale University

Jorge Galan and his colleagues in the Section of Microbial Pathogenesis at the Yale School of Medicine report a new and fundamental mechanism that Salmonella bacteria use to replicate within body cells and cause disease without endangering themselves. The work appears in the June 18 issue of Science.

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.
15 June 2004

Olfactory system matures in different stages

Full development of the sense of smell in mammals is dependent on functional activity during critical periods in development, according to a study by researchers at Yale, Rockefeller and Columbia Universities and published in the journal, Science.

In mammals, the connection between odor and the brain occurs over a single nerve connection. The olfactory sensory neurons that have the same odorant receptor are directed to regions of the olfactory bulb, where they coalesce into a single structure, a glomerulus. This process is molecularly determined, but it remains controversial to what extent the process also relies on stimulation from the outside.

The visual system, it is known, develops initially without any functional activity, but is later refined and polished through sensory activity. Charles Greer, professor of neurosurgery at Yale, and his collaborators. examined the postnatal formation of glomeruli in odor receptors M71 and M72 in gene-targeted mice during development to determine whether the same development process is found in the olfactory system.

The results of the study established four principles of olfactory system development, without sensory activity there is no full maturation; there is a sensitive period during which activity influences the maturation of the organization; sensitive periods occur at different times for different olfactory receptors; and glomeruli may be innervated by more than one kind of sensory nerve during early development.

The lead author on the paper was Dong-Jing Zou of Columbia. Co-authors included Paul Feinstein and Peter Mombaerts of Rockefeller University; Aimee Rivers, Glennis Matthews, Ann Kim and Stuart Feinstein, from Columbia.

http://www.yale.edu

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