Bacteria recognize antimicrobials, respond with counter-defenses

Main Category: MRSA / Drug Resistance
Article Date: 20 Aug 2005 - 0:00 PDT

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Findings may lead to ways to get around bacterial resistance -

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

University of Washington (UW) and McGill University researchers have revealed a molecular mechanism whereby bacteria can recognize tiny antimicrobial peptide molecules, then respond by becoming more virulent. Their studies were done on the bacterium Salmonella typhimurium. The findings were published in the Aug. 12 edition of Cell.

Salmonella typhimurium can contaminate meats such as beef, pork, chicken, as well 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 organism fights back against the immune system may lead to treatments that get around bacterial resistance.

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

Strangely enough, the same molecules that the body sends out to help destroy salmonella inadvertently launch bacterial defenses. It is as if missiles armed, rather than demolished, the target. The body's antimicrobial peptides bind to an enzyme, PhoQ, that acts as a watchtower and interceptor near the surface of bacteria 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 genes are responsible for products that fortify the bacterial cell surface and protect the bacteria from being killed.

The research was done in the UW laboratory of Dr. Samuel Miller, professor of microbiology and of medicine, Division of Infectious Diseases. The Miller Lab explores the 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 UW senior fellow in microbiology and genome sciences. The research team, under the direction of Miller, included Dr. Sarah Sanowar of the Department of Microbiology and Immunology at McGill University; Dr. Margaret Daley, a UW senior fellow in biochemistry; Anna Schneider, a UW undergraduate majoring in mathematics and biochemistry; Uhn Soo Cho, a graduate student in biological structure; Dr. Wenqing Xu, assistant professor of biological structure; Dr. Rachel Klevit, professor of biochemistry; and Dr. Herve Le Moual on the McGill Faculty of Dentistry.

Grants from National Institute of Allergy and Infectious Diseases and from the Canadian Institutes of Health Research funded the study.

Leila Gray
leilag@u.washington.edu
206-685-0381
University of Washington
http://www.uwnews.org

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