Bacteria Recognize Antimicrobials, Respond With Counter-defenses

University ofWashington (UW) and McGill researchers have revealed a molecularmechanism whereby bacteria can recognize tiny antimicrobial peptidemolecules, then respond by becoming more virulent. Their studies weredone on the bacterium Salmonella typhimurium. The findings werepublished in the Aug. 12 edition of the journal Cell.

Salmonellatyphimurium 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 behindthe increase of salmonellosis in people. Some food science institutesanticipate that virulent strains of salmonella will become more commonthroughout 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 misslesarmed, rather than demolished, the target. The body's antimicrobialpeptides bind to an enzyme, PhoQ, which acts as a watchtower andinterceptor near the surface of bacterial cell membranes. The peptidebinding activates PhoQ, which sets off a cascade of signals. Thesignals 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 howdisease-causing bacteria interact with cells in the host they haveinfected, and adapt to environments inside the body, such as the airway.

Thelead 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.