NEITHER THE BVG(-) PHASE NOR THE VRG6 LOCUS OF BORDETELLA-PERTUSSIS IS REQUIRED FOR RESPIRATORY-INFECTION IN MICE

In Bordetella species, the BvgAS sensory transduction system mediates an alteration between the Bvg(+) phase, characterized by expression of adhesins and toxins, and the Bvg(-) phase, characterized by the expre ssion of motility and coregulated phenotypes in Bordetella bronchisept ica and by the expression of vrg loci in Bordetella pertussis. Since t here is no known environmental or animal reservoir for B. pertussis, t he causative agent of whooping cough, it has been assumed that this ph enotypic alteration must occur within the human host during infection. Consistent with this hypothesis was the observation that a B. pertuss is mutant, SK6, containing a TnphoA insertion mutation in a Bvg-repres sed gene (vrg6) was defective for tracheal and lung colonization in a mouse model of respiratory infection (D. T. Beattie, R. Shahin, and J. Mekalanos, Infect. Immun. 60:571-577, 1992). This result was inconsis tent, however, with the observation that a Bvg(+) phase-locked B. bron chiseptica mutant was indistinguishable from the wild type in its abil ity to establish a persistent respiratory infection in rabbits and rat s (P. A. Cotter and J. F. Miller, Infect. Immun. 62:3381-3390, 1994; B . J. Akerley, P. A. Cotter, and J. F. Miller, Cell 80:611-620, 1995). To directly address the role of Bvg-mediated signal transduction in B. pertussis pathogenesis, we constructed Bvg(+) and Bvg(-) phase-locked mutants and compared them with the wild type for their ability to col onize the respiratory tracts of mice. Our results show that the Bvg(+) phase of B. pertussis is necessary and sufficient for respiratory inf ection. By constructing a strain with a deletion in the bvgR regulator y locus, we also show that ectopic expression of Bvg(-) phase phenotyp es decreases the efficiency of colonization, underscoring the importan ce of Bvg-mediated repression of gene expression in vivo. Finally, we show that the virulence defect present in strain SK6 cannot be attribu ted to the vrg6 mutation. These data contradict an in vivo role for th e Bvg(-) phase of B. pertussis.