Strain-dependent role of BrkA during Bordetella pertussis infection of the murine respiratory tract.

Bordetella pertussis, the causative agent of whooping cough, expresses many virulence factors believed to be involved in infection and disease progression. While these factors as a group are required for infection, deletion of individual virulence factor genes generally has limited effects on the ability of B. pertussis to efficiently infect the respiratory tract of mice, suggesting they may perform noncritical or redundant functions. We have recently observed that a B. pertussis strain, putatively with a mutation of a single gene, brkA, results in a severe defect in vivo. Although BrkA has been shown to be required for B. pertussis to resist complement-mediated killing in vitro, the relevance of these findings to the in vivo role of BrkA during infection has not been examined. Transducing this mutation into multiple wild-type B. pertussis strains allowed us to confirm the in vitro phenotype of reduced resistance to serum complement. All DeltabrkA mutants were increased in their sensitivity to complement in vitro, both in the presence and absence of antibodies. However, these strains differed substantially in their phenotypes in vivo. DeltabrkA mutants of recent clinical isolates were indistinguishable from wild-type strains in their efficient infection of respiratory organs, suggesting that the function of BrkA in these strains is noncritical or redundant. In contrast, multiple DeltabrkA strains derived from Tohama I were severely defective during the first week postinoculation compared to their wild-type parent. This defect was present even in complement-deficient mice, revealing a complement-independent phenotype for the DeltabrkA mutant in respiratory tract infection.