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 that may orchestrate the transition from acute colonization to chronic infection in this important human pathogen," explains Dr. Lory. Further, the observation that a number of genes with no known function are regulated by RetS in coordination with established virulence determinants suggests that these genes may code for previously undiscovered virulence factors.
Andrew Goodman, Bridget Kulasekara, Arne Rietsch, Dana Boyd, Roger Smith, and Stephen Lory: "A Signaling Network Reciprocally Regulates Genes Associated with Acute Infection and Chronic Persistence in Pseudomonas aeruginosa"
Publishing in Developmental Cell, Volume 7, Number 5, November 2004, pages 745-754.