Differential regulation of Bvg-activated virulence factors plays a role inBordetella pertussis pathogenicity

Bordetella pertussis, the causative agent of whooping cough, regulates expr ession of many virulence factors via a two component signal transduction sy stem encoded by the bvgAS regulatory locus. It has been shown by transcript ion activation kinetics that several of the virulence factors are different ially regulated. fha is transcribed within 10 min following a bvgAS-inducin g signal, while pm is transcribed after 1 h and ptx is not transcribed unti l 2 to 4 h after induction. These genes therefore represent early, intermed iate, and late classes of bvg-activated promoters, respectively. Although t here have been many insightful studies into the mechanisms of BvgAS-mediate d regulation, the role that differential regulation of virulence genes play s in B. pertussis pathogenicity has not been characterized. We provide evid ence that alterations to the promoter regions of bvg-activated genes can al ter the kinetic pattern of expression of these genes without changing stead y-state transcription levels. In addition, B. pertussis strains containing these promoter alterations that express either ptx at an early time or fha at a late time demonstrate a significant reduction in their ability to colo nize respiratory tracts in an intranasal mouse model of infection. These da ta suggest a role for differential regulation of bvg-activated genes, and t herefore for the BvgAS regulatory system, in the pathogenicity of B. pertus sis.