title: Microbial pathogenesis in cystic fibrosis: co-ordinate regulation of heat-shock response and conversion to mucoidy in Pseudomonas aeruginosa.
abstract: Conversion of Pseudomonas aeruginosa to the mucoid phenotype plays a major role in the pathogenesis of respiratory infections in cystic fibrosis (CF). One mechanism responsible for mucoidy is based on mutations that inactivate the anti-sigma factor, MucA, which normally inhibits the alternative sigma factor, AIgU. The loss of MucA allows AIgU to freely direct transcription of the genes responsible for the production of the exopolysaccharide alginate resulting in mucoid colony morphology. In Escherichia coli, a close homologue of AIgU, sigma(E), directs transcription of several genes under conditions of extreme heat shock. Here we examined whether AIgU, besides its role in controlling alginate production, affects the heat-shock response in P. aeruginosa. The P. aeruginosa rpoH gene encoding a homologue of the major heat-shock sigma factor, sigma32, was found to be transcribed by AIgU containing RNA polymerase from one of its promoters (P3) identified in this study. Transcription of rpoH from P3 was elevated upon exposure to extreme heat shock in an aIgU-dependent manner. Importantly, the AIgU-dependent promoter of rpoH was found to be activated in mucoid mucA mutants. In keeping with this observation, introduction of a wild-type mucA gene abrogated AIgU-dependent rpoH transcription in mucoid P. aeruginosa laboratory isolates and CF isolates. These results suggest that conversion to mucoidy and the heat-shock response are co-ordinately regulated in P. aeruginosa. The simultaneous activation of both systems in mucA mutants, selected in the lungs of CF patients, may have significance for the inflammatory processes characteristic of the establishment of chronic infection and ensuing clinical deterioration in CF.
authors.affiliation: Department of Microbiology and Immunology, The University of Michigan Medical School, Ann Arbor 48109-0620, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Schurr
authors.forename: V
authors.initials: V
authors.lastname: Deretic
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002874:Chromosome Mapping; D003550:Cystic Fibrosis / Q000382:microbiology*; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D014644:Genetic Variation; D006360:Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism*; D018869:Heat-Shock Response / Q000235:genetics*; D006801:Humans; D008171:Lung Diseases / Q000382:microbiology; D011401:Promoter Regions, Genetic; D011550:Pseudomonas aeruginosa / Q000235:genetics* / Q000378:metabolism* / Q000472:pathogenicity; D012808:Sigma Factor / Q000235:genetics* / Q000378:metabolism*; D014157:Transcription Factors; D014158:Transcription, Genetic
chemical_list: C079619:AlgU protein, Pseudomonas aeruginosa; D001426:Bacterial Proteins; D006360:Heat-Shock Proteins; C063757:MucA protein, Bacteria; D012808:Sigma Factor; D014157:Transcription Factors; C069774:heat-shock sigma factor 32; D012321:DNA-Directed RNA Polymerases