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Bacteria Recognize Antimicrobials, Respond With Counter-defenses

Many living things, from fruit flies to people, naturallyproduce disease-fighting chemicals, called antimicrobial peptides, to kill harmful bacteria. In a counter move, some disease-causing bacteria have evolved microbial detectors. The bacteria sense the presence of antimicrobial peptides as a warning signal. The alarm sets off areaction inside the bacteria to avoid destruction.

Salmonella typhimurium can contaminate meats such as beef, pork, and chicken, aswell as cereals and other foods, and cause severe intestinal illness.Certain strains of the bacteria are difficult to treat, and are behind the increase of salmonellosis in people. Some food science institutes anticipate that virulent strains of salmonella will become more common throughout the food chain. Learning how this sometimes deadly organismfights back against the immune system may lead to treatments that getaround bacterial resistance.

Work in this area may also suggestways other disease-causing Gram-negative bacteria maintain a strongholdin the midst of the body's attempts to get rid of them.

Strangelyenough, the same molecules that the body sends out to help destroysalmonella inadvertently launch bacterial defenses. It is as if missles armed, rather than demolished, the target. The body's antimicrobial peptides bind to an enzyme, PhoQ, which acts as a watch tower and interceptor near the surface of bacterial cell membranes. The peptide binding activates PhoQ, which sets off a cascade of signals. The signals turn on a large set of bacterial genes. Some of the genes areresponsible for products that fortify the bacterial cell surface andprotect the bacteria from being killed.

The research was done inthe UW laboratory of Dr. Samuel Miller, professor of microbiology andof medicine, Division of Infectious Diseases. The MIller Lab exploresthe molecular aspects of bacteria-induced illness, and how disease-causing bacteria interact with cells in the host they have infected, and adapt to environments inside the body, such as the airway.

The lead author of the Aug.12 Cell article was Dr. Martin Bader, a UWsenior fellow in microbiology and genome sciences. The research team,under the direction of Miller, included Dr. Sarah Sanowar of theDepartment of Microbiology and Immunology at McGill University; Dr.Margaret Daley, a UW senior fellow in biochemistry; Anna SChneider, aUW undergraduate majoring in mathematics and biochemistry; Uhn Soo Cho,a graduate studenty in biological structure; Dr. Wenqing Xu, assistantprofessor of biological structure; Dr. Rachel Klevit, professor ofbiochemistry; and Dr. Herve Le Moual on the McGill Faculty of Dentistry.

Grantsfrom the National Institute of Allergy and Infectious Diseases and fromthe Canadian Institutes of Health Research funded the study.

University of Washington. August 2005.