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Molecular switch provides clues to remarkable adaptability of human pathogen

Scientists have identified a gene that may play a key role in the ability of an important human pathogen to sense and adjust to its surroundings. The research, published in the November issue of Developmental Cell, provides new evidence about how bacteria regulate gene expression in response to changing environmental conditions to promote adaptation and long-term survival.

Pseudomonas aeruginosa is frequently found in soil, water, plants, and animals and can thrive in a wide variety of environments. P. aeruginosa also causes a variety of potentially fatal infections in humans with a disease- or injury-weakened immune system. In addition, infection with P. aeruginosa is the primary cause of death for patients with cystic fibrosis (CF), who often become infected shortly after birth and are afflicted with chronic persistent infection throughout their lives.

Dr. Stephen Lory and colleagues from the Department of Microbiology and Molecular Genetics at Harvard Medical School demonstrated that a P. aeruginosa gene product, called RetS, activates multiple genes known to be involved in host cell contact-dependent toxin secretion and mobility, processes required for acute infection. The researchers demonstrated that mice develop pneumonia after exposure to normal P. aeruginosa but are resistant to infection with a mutant variant of P. aeruginosa lacking RetS. Surprisingly, the less virulent P. aeruginosa with mutated RetS formed bacterial communities, called biofilms, much earlier than the normal bacteria. Formation of biofilms is associated with long-term chronic infection. The researchers used transcriptional profiling to show that RetS inhibited a collection of genes known to promote biofilm formation.

The researchers conclude that RetS activates multiple virulence factors that contribute to acute infection while simultaneously repressing those required for long-term, chronic infection. "This system functions as a multicomponent switch tha
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Contact: Heidi Hardman
hhardman@cell.com
617-397-2879
Cell Press
8-Nov-2004


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