Contribution of regulation by the bvg locus to respiratory infection of mice by Bordetella pertussis.
Whooping cough is an acute respiratory disease caused by the small, gram-negative bacterium Bordetella pertussis. B. pertussis expresses several factors that contribute to its ability to cause disease. These factors include surface-associated molecules, which are involved in the adherence of the organism to respiratory epithelial cells, as well as several extracellular toxins that inhibit host defenses and induce damage to host tissues. The expression of virulence factors in B. pertussis is dependent upon the bvg locus, which consists of three genes: bvgA, bvgS, and bvgR. The bvgAS genes encode a two-component regulatory system consisting of a sensor protein, BvgS, and a transcriptional activator, BvgA. Upon modification by BvgS, BvgA binds to the promoter regions of the bvg-activated genes and activates transcription. One of the bvg-activated genes, bvgR, is responsible for the regulation of the bvg-repressed genes, the functions of which are unknown. The fact that these genes are regulated by the bvg locus suggests that they play a role in the pathogenesis of the bacterium. In order to evaluate the contribution of bvg-mediated regulation to the virulence of B. pertussis and determine if expression of the bvg-repressed genes is required for the virulence of B. pertussis, we examined the ability of B. pertussis mutants, defective in their ability to regulate the expression of the bvg-activated and/or the bvg-repressed genes, to cause disease in the mouse aerosol challenge model. Our results indicate that the bvgR-mediated regulation of gene expression contributes to respiratory infection of mice.
Merkel
T J
TJ
National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892, USA. merkel@yoda.nidr.nih.gov
Stibitz
S
S
Keith
J M
JM
Leef
M
M
Shahin
R
R
D018829:Adhesins, Bacterial / Q000378:metabolism; D000336:Aerosols; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology*; D001886:Bordetella pertussis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004195:Disease Models, Animal; D015964:Gene Expression Regulation, Bacterial; D006388:Hemagglutinins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010940:Plant Proteins / Q000235:genetics / Q000502:physiology*; D011817:Rabbits; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014774:Virulence / Q000235:genetics; D010566:Virulence Factors, Bordetella / Q000378:metabolism; D014917:Whooping Cough / Q000378:metabolism / Q000382:microbiology*
D018829:Adhesins, Bacterial; D000336:Aerosols; D001426:Bacterial Proteins; C099900:Bvg protein, Beta vulgaris; C065601:BvgA protein, Bacteria; D006388:Hemagglutinins; D010940:Plant Proteins; D014157:Transcription Factors; D010566:Virulence Factors, Bordetella; C080662:bvgS protein, Bordetella pertussis; C065273:filamentous hemagglutinin adhesin, Bordetella pertussis