A PHASE VARIANT OF BORDETELLA-PERTUSSIS WITH A MUTATION IN A NEW LOCUS INVOLVED IN THE REGULATION OF PERTUSSIS TOXIN AND ADENYLATE-CYCLASE TOXIN EXPRESSION

A novel nonhemolytic phase variant of Bordetella pertussis was charact erized. This strain is strongly impaired in the transcription of the p ertussis and adenylate cyclase toxins, whereas other known virulence-r elated factors such as the filamentous hemagglutinin, the fimbriae, an d the outer membrane protein pertactin are expressed and regulated nor mally. Complementation and allelic exchange experiments demonstrated t hat the mutation is localized neither in the bvg locus involved in vir ulence regulation nor in the genes responsible for synthesis and trans port of the toxins pertussis and adenylate cyclase. Instead, the mutat ion impairing transcription of at least the two toxin genes is located in a new genetic locus, which acts together with the BvgA/S two-compo nent regulatory system on the expression of a subset of virulence gene s. Further analysis suggested that most presumably the mutation affect s a sequence-specific DNA-binding protein which contributes to transcr iptional activation. The mutant was nonlethal in a murine respiratory model, which corresponds well with the lack of expression of the toxin s. However, the clearing rate of this mutant from the lungs of mice wa s much lower than that of a bvg mutant, suggesting that factors other than the toxins may play a role in the persistence of the bacteria in the respiratory tract of mice.