title: The Pseudomonas aeruginosa homologs of hemC and hemD are linked to the gene encoding the regulator of mucoidy AlgR.
abstract: The algD gene encodes NAD-linked GDPmannose dehydrogenase, which is essential for the mucoid phenotype, an important virulence factor expressed by Pseudomonas aeruginosa in cystic fibrosis patients. AlgR, a response regulator controlling mucoidy, is required for high level expression of algD. Inactivation of algR completely abrogates algD expression while mutations immediately downstream of algR affect induction of the algD promoter. In order to examine the nature of genetic elements located downstream of algR, the complete nucleotide sequence of this region was determined. This analysis revealed the presence of two newly identified P. aeruginosa genes with predicted gene products homologous to known porphobilinogen deaminases (HemC) from other organisms, and uroporphyrinogen III cosynthase (HemD) from Escherichia coli. The concerted action of both of these enzymes is essential for the synthesis of heme precursors. Mutations within the region containing the P. aeruginosa homologs of hemC and hemD affect algD promoter activity during growth on nitrate. Furthermore, transcriptional analyses indicated that hemC was cotranscribed with algR at detectable levels in mucoid cells. These results suggest a link between physiological processes dependent on heme and conditions conductive to algD expression and mucoidy.
authors.affiliation: Department of Microbiology, University of Texas Health Science Center, San Antonio 78284-7758.
authors.forename: C D
authors.initials: CD
authors.lastname: Mohr
authors.forename: S K
authors.initials: SK
authors.lastname: Sonsteby
authors.forename: V
authors.initials: V
authors.lastname: Deretic
mesh_terms: D000464:Alginates / Q000378:metabolism; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics; D001483:Base Sequence; D002237:Carbohydrate Dehydrogenases / Q000235:genetics; D003550:Cystic Fibrosis / Q000382:microbiology; D004269:DNA, Bacterial / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics; D029968:Escherichia coli Proteins; D005798:Genes, Bacterial; D005809:Genes, Regulator; D008040:Genetic Linkage; D020723:Glucuronic Acid; D006603:Hexuronic Acids; D006801:Humans; D011163:Hydroxymethylbilane Synthase / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D011550:Pseudomonas aeruginosa / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D014576:Uroporphyrinogen III Synthetase / Q000235:genetics
chemical_list: D000464:Alginates; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D029968:Escherichia coli Proteins; D006603:Hexuronic Acids; D020723:Glucuronic Acid; D002237:Carbohydrate Dehydrogenases; C020562:GDPmannose dehydrogenase; D011163:Hydroxymethylbilane Synthase; C073160:hemC protein, E coli; D014576:Uroporphyrinogen III Synthetase