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http://www.eurekalert.org/pub_releases/ ... 071108.php

Berkeley -- Disease-causing microbes like the food-borne bacterium Listeria monocytogenes specialize in invading and replicating inside their animal hosts' own cells, making them particularly tricky to defeat. Now, a new study led by biologists at the University of California, Berkeley, has identified a molecular alarm system in which the intracellular pathogen sends out signals that kick the immune response into gear.

The findings, to be reported the week of July 14 in the journal Proceedings of the National Academy of Sciences, shed light on how the cells recognize and destroy the pathogenic bugs living within their walls, and may even provide new targets for the research and development of new vaccines and drugs.

The pathogens' signals come from multidrug resistance transporters (MDRs), membrane proteins used by a wide variety of organisms to pump out a broad range of molecules from their systems. Similar transporters have been linked in other studies to the development of resistance to multiple drugs that are toxic to the pathogen. This study is the first to connect multidrug resistance transporters directly to stimulation of the immune system, although the nature of the molecules that the bacteria are spitting out remains unclear.

"For the MDRs to work, the pathogen needs to be alive, so this study actually shows how the immune system can tell the difference between a living, harmful microbe and one that is dead," said the study's principal investigator, Daniel Portnoy, a UC Berkeley professor with joint appointments in the Department of Molecular and Cell Biology and the School of Public Health, and associate director of the Berkeley Center for Emerging and Neglected Diseases. "This is important because you don't want the immune system to overreact to non-threats, which is what happens in autoimmune disorders such as inflammatory bowel disease, asthma and multiple sclerosis."