The primary focus of work in our laboratory has been the vir locus of Bordetella pertussis. This locus is responsible for the regulation of B. pertussis virulence determinants (pertussis toxin, filamentous hemagglutinin, etc.) in response to environmental stimuli. This locus is also the site of a reversible frameshift mutation which results in the phenomenon of phase variation. In the past we had observed that two closely related strains of B. pertussis underwent phase variation at dramatically different rates. We have recently extended this observation by constructing a defined frameshift mutation in a kanamycin resistance gene and showing that the reversion of this mutation also occurs at dramatically different rates in these two strains. We are currently engaged in the genetic mapping of this hypermutable phenotype, with an eye to the isolation of the gene(s) responsible. This mapping is made possible because we have recently completed a physical map of the B. pertussis chromosome. Physical mapping of previously isolated genes is a simple and straightforward task, and we have several collaborations with other workers in the field to map specific genes. However, the derivation of this map also allows the use of genetic tools for mapping. Specifically, we have designed and constructed new strains and new vectors which allow us to do genetic mapping using Hfr-like strains of B. pertussis. Such an approach will allow the isolation of some interesting genes which has not been possible using standard cloning techniques. The primary scientific finding of the chromosomal map was that the genes for B. pertussis virulence determinants are unlinked, i.e. are scattered around the chromosome. The implications of this finding are currently being extended by constructing maps of other strains of B. pertussis and other species of Bordetella with the hopes of further defining their evolutionary relationships.

National Institute of Health (NIH)
Food and Drug Administration (FDA)
Intramural Research (Z01)
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