In patients with cystic fibrosis, chronic infection with the pathogen Pseudomonas aeruginosa is the primary cause of death. During the course of such long-lasting infections, the bacteria respond to their environment, first expressing a set of genes optimal for early infection and colonization and later expressing components that favor formation of biofilms that allow aggregation of the bacteria and protection from host defenses. Goodman et al. screened for two-component system proteins (histidine kinase sensors or phosphate receiver response regulators) that might participate in control of the gene expression programs that mediate the distinct properties of the bacteria during early or late infection. They isolated a gene named retS (for regulator of exopolysaccharide and type III secretion). Transcriptional profiling showed that expression of retS enhanced expression of genes encoding virulence factors and decreased expression of genes that enhance synthesis of exopolysaccharides, cell surface components that support formation of biofilms. RetS thus appears to be a primary regulator of the phenotypic transition from early to late infection. The RetS protein has a very unusual structure in that it contains two dissimilar response regulator receiver domains and lacks a histidine phosphotransfer domain. The authors propose that one or both of the receiver domains may respond to phosphorylation by proteins other than RetS itself, thus allowing RetS to provide coordination of multiple inputs that coordinate the phenotypic response.
A. L. Goodman, B. Kulasekara, A. Rietsch, D. Boyd, R. S. Smith, S. Lory, A signaling network reciprocally regulates genes associated with acute infection and chronic persistence in Pseudomonas aeruginosa. Developmental Cell 7, 745-754 (2004). [Online Journal]