Mutations in the bvgA gene of Bordetella pertussis that differentially affect regulation of virulence determinants.
By using chemical mutagenesis and genetic mapping, a search was undertaken for previously undescribed genes which may be involved in different regulatory mechanisms governing different virulence factors of Bordetella pertussis. Previous studies have shown that the fha locus encoding filamentous hemagglutinin is regulated directly by the bvgAS two component system, while regulation of ptx encoding pertussis toxin is less direct or occurs by a different mechanism. With a strain containing gene fusions to each of these regulated loci, screening was done for mutations which were defective for ptx expression but maintained normal or nearly normal levels of fha expression. Two mutations which had such a phenotype and were also deficient in adenylate cyclase toxin/hemolysin expression were found and characterized more fully. Both were found to affect residues in the C-terminal portion of the BvgA response regulator protein, a domain which shares sequence similarity with a family of regulatory proteins including FixJ, UhpA, MalT, RcsA, RcsB, and LuxR. The residues affected are within a region which, by extension from studies on the LuxR protein, may be involved in transcriptional activation.
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Division of Bacterial Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892.
D037361:Adenylate Cyclase Toxin; D000595:Amino Acid Sequence; D001425:Bacterial Outer Membrane Proteins / Q000032:analysis; D001426:Bacterial Proteins / Q000032:analysis / Q000235:genetics*; D001483:Base Sequence; D001886:Bordetella pertussis / Q000235:genetics* / Q000472:pathogenicity; D004252:DNA Mutational Analysis; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics*; D005809:Genes, Regulator / Q000235:genetics*; D006388:Hemagglutinins / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D037342:Pertussis Toxin; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D015183:Restriction Mapping; D014157:Transcription Factors / Q000235:genetics*; D014774:Virulence; D010566:Virulence Factors, Bordetella / Q000032:analysis / Q000235:genetics
D037361:Adenylate Cyclase Toxin; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; C065601:BvgA protein, Bacteria; D006388:Hemagglutinins; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D010566:Virulence Factors, Bordetella; C068929:pertactin; D037342:Pertussis Toxin