Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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The effect of pertussis toxin on lung airway gene expression during B. pertussis infection in mice

ABSTRACT: Genome-wide expression analysis of mouse lung responses to Bordetella pertussis infection and the effects of pertussis toxin Total lung RNA from wild-type and pertussis toxin-defficient B. pertussis-infected mice at two and four days post inoculation compared to control, mock-infected mice. Seven-week old female BALB/c mice were intranasally inoculated with 1 x 106 CFU WT B. pertussis (Tohama I), 1 x 106 CFU ΔPT (WT carrying a PT deletion), or 30 x 106 CFU of the ΔPT strain. Whole lung tissue was collected from mice sacrificed at 2 and 4 days post inoculation (n = 3 per group per time point). Control mice were inoculated with PBS and sacrificed 2 days post inoculation (n = 2).

ORGANISM(S): Mus musculus

SUBMITTER: Nicholas Carbonetti

PROVIDER: E-GEOD-33995 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Pertussis is a highly contagious, acute respiratory disease in humans caused by the Gram-negative pathogen Bordetella pertussis. Pertussis has resurged in the face of intensive vaccination and this has coincided with the emergence of strains carrying a particular allele for the pertussis toxin promoter, ptxP3, which is associated with higher levels of pertussis toxin (Ptx) production. Within 10 to 20 years, ptxP3 strains have nearly completely replaced the previously dominant ptxP1 strains resulting in a worldwide selective sweep. In order to identify B. pertussis genes associated with the selective sweep, we compared the expression of genes in ptxP1 and ptxP3 strains that are under control of the Bordetella master virulence regulatory locus (bvgASR). The BvgAS proteins comprise a two component sensory transduction system which is regulated by temperature, nicotinic acid and sulfate. By increasing the sulfate concentration, it is possible to change the phase of B. pertussis from virulent to avirulent. Until recently, the only distinctive phenotype of ptxP3 strains was a higher Ptx production. Here we identify additional phenotypic differences between ptxP1 and ptxP3 strains which may have contributed to its global spread by comparing global transcriptional responses under sulfate-modulating conditions. We show that ptxP3 strains are less sensitive to sulfate-mediated gene suppression, resulting in an increased production of the vaccine antigens pertactin (Prn) and Ptx and a number of other virulence genes, including a type III secretion toxin, Vag8, a protein involved in complement resistance, and lpxE involved in lipid A modification. Furthermore, enhanced expression of the vaccine antigens Ptx and Prn by ptxP3 strains was confirmed at the protein level. Identification of genes differentially expressed between ptxP1 and ptxP3 strains may elucidate how B. pertussis has adapted to vaccination and allow the improvement of pertussis vaccines by identifying novel vaccine candidates.

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The effect of pertussis toxin on lung airway gene expression during B. pertussis infection in mice

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