title: Stationary phase-specific virulence factor overproduction by a lasR mutant of Pseudomonas aeruginosa.
abstract: Secreted virulence factors of the human pathogen Pseudomonas aeruginosa are often under quorum sensing control. Cells lacking the quorum-sensing regulator LasR show reduced virulence factor production under typical laboratory conditions and are hypo-virulent in short-term animal infection models, yet lasR mutants are frequently associated with long-term infection in cystic fibrosis patients. Here, I show that in stationary-phase or slow-growth conditions, lasR cells continuously and strongly produce the important virulence factor pyocyanin while wild-type cells do not. Pyocyanin overproduction by lasR cells is permitted by loss of repression by RsaL, a LasR-dependent negative regulator. lasR cells also contribute pyocyanin in mixed cultures, even under "cheating" conditions where they depend on their wild-type neighbors for nutrients. Finally, some clinical P. aeruginosa isolates with lasR mutations can overproduce pyocyanin in the laboratory. These results imply that slow-growing clinical populations of lasR cells in chronic infections may contribute to virulence by producing pyocyanin under conditions where lasR⁺ cells do not.
authors.affiliation: Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts, United States of America.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Cabeen
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D009154:Mutation; D010641:Phenotype; D011550:Pseudomonas aeruginosa / Q000166:cytology / Q000235:genetics* / Q000378:metabolism*; D011710:Pyocyanine / Q000096:biosynthesis*; D053038:Quorum Sensing; D012097:Repressor Proteins / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics*; D037521:Virulence Factors / Q000096:biosynthesis*
chemical_list: D001426:Bacterial Proteins; C080365:LasR protein, Pseudomonas aeruginosa; D012097:Repressor Proteins; D015534:Trans-Activators; D037521:Virulence Factors; C118377:rsaL protein, Pseudomonas aeruginosa; D011710:Pyocyanine