Mucoid Pseudomonas aeruginosa in cystic fibrosis: mutations in the muc loci affect transcription of the algR and algD genes in response to environmental stimuli.
Increased levels of alginate biosynthesis cause mucoidy in Pseudomonas aeruginosa, a virulence factor of particular importance in cystic fibrosis. The algR gene product, which controls transcription of a key alginate biosynthetic gene, algD, is homologous to the activator members of the two-component, environmentally responsive systems (NtrC, OmpR, PhoB, ArcA, etc). In this report, we show that mutations in the muc loci, (muc-2, muc-22, and muc-23, in the standard genetic P. aeruginosa strain PAO, as well as a mapped muc allele in an isolate from a cystic fibrosis patient) affect transcription of algD and algR. This influence was strongly dependent on environmental factors. Regulation by nitrogen was observed in all strains examined, but the absolute transcriptional levels, determining the mucoid or nonmucoid status, were strain (muc allele)-dependent. Increased concentrations of NaCl in the medium, an osmolyte which is elevated in cystic fibrosis lung secretions, resulted in an increased algD transcription and mucoid phenotype in a muc-2 strain; the same conditions, however, produced a nonmucoid phenotype in the muc-23 background and abolished algD transcription. Mutations in the muc loci may cause mucoidy by deregulating the normal response of the alginate system to environmental stimuli.
Deretic
V
V
Department of Microbiology, University of Texas Health Science Center, San Antonio 78284-7758.
Govan
J R
JR
Konyecsni
W M
WM
Martin
D W
DW
D000464:Alginates / Q000378:metabolism; D002237:Carbohydrate Dehydrogenases / Q000235:genetics*; D003550:Cystic Fibrosis / Q000382:microbiology*; D015964:Gene Expression Regulation, Bacterial; D006025:Glycosaminoglycans / Q000096:biosynthesis*; D006801:Humans; D009154:Mutation; D009584:Nitrogen / Q000378:metabolism; D011135:Polysaccharides, Bacterial / Q000096:biosynthesis*; D011401:Promoter Regions, Genetic; D011550:Pseudomonas aeruginosa / Q000201:enzymology / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
D000464:Alginates; D006025:Glycosaminoglycans; D011135:Polysaccharides, Bacterial; D014157:Transcription Factors; C046129:mucoid exopolysaccharide (P aeruginosa); D002237:Carbohydrate Dehydrogenases; C020562:GDPmannose dehydrogenase; D009584:Nitrogen