title: A signaling network reciprocally regulates genes associated with acute infection and chronic persistence in Pseudomonas aeruginosa.
abstract: The opportunistic pathogen Pseudomonas aeruginosa causes a variety of acute and chronic infections. We identified a gene whose inactivation results in attenuation of virulence due to premature activation of genes involved in biofilm formation and coordinate repression of genes required for initial colonization. This gene, retS, encodes a hybrid sensor kinase/response regulator with an unconventional arrangement of functional domains. Genome-wide transcriptional profiling indicates that the retS gene is required for expression of the Type III secretion system and other virulence factors and for repression of genes responsible for exopolysaccharide components of the P. aeruginosa biofilm matrix. These disparate phenotypes are suppressed by transposon insertions in genes encoding the GacS/GacA/rsmZ signal transduction pathway, a highly conserved system involved in the control of diverse adaptive functions. This study defines RetS as a pleiotropic regulator of multiple virulence phenotypes that orchestrates genes required for acute infection and genes associated with chronic persistence.
authors.affiliation: Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Goodman
authors.forename: Bridget
authors.initials: B
authors.lastname: Kulasekara
authors.forename: Arne
authors.initials: A
authors.lastname: Rietsch
authors.forename: Dana
authors.initials: D
authors.lastname: Boyd
authors.forename: Roger S
authors.initials: RS
authors.lastname: Smith
authors.forename: Stephen
authors.initials: S
authors.lastname: Lory
mesh_terms: D000208:Acute Disease; D000818:Animals; D001426:Bacterial Proteins / Q000502:physiology; D018441:Biofilms; D016466:CHO Cells; D002908:Chronic Disease; D006224:Cricetinae; D003412:Cricetulus; D003470:Culture Media / Q000633:toxicity; D004251:DNA Transposable Elements; D005260:Female; D017353:Gene Deletion; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D005809:Genes, Regulator; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D016254:Mutagenesis, Insertional; D011552:Pseudomonas Infections / Q000235:genetics* / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism / Q000472:pathogenicity* / Q000502:physiology; D015398:Signal Transduction; D014774:Virulence; D037521:Virulence Factors
chemical_list: D001426:Bacterial Proteins; D003470:Culture Media; D004251:DNA Transposable Elements; D037521:Virulence Factors