<Emphasis Type="Italic">bvg</Emphasis>-Negative Regulation of Repeated Sequence Transposition in <Emphasis Type="Italic">Bordetella pertussis</Emphasis> Cells

A method of monitoring the sequential events of IS481 transposition into the ctag site of bvg operon of Bordetella pertussis has been developed. Reproduction of virulent B. pertussis cells in vitro is accompanied by intrachromosomal site-specific IS481 transposition, which, in turn, results in inactivation of bvg operon of the causative agent and cell avirulent state. Avirulent bvg mutants of B. pertussis are incapable of intramolecular IS481 transposition. The frequency of the transposition increases when MgSO₄ and nicotinic acid are present the culture medium. In the absence of these modulating factors, IS481 transposition along B. pertussis chromosome is inhibited but not arrested completely. Negative regulation of the bvg-repressed genes of B. pertussis seems to be a mechanism that controls bvg-dependent IS481 transposition.     

Bacterial DNA topology and infectious disease

The Gram-negative bacterium Escherichia coli and its close relative Salmonella enterica have made important contributions historically to our understanding of how bacteria control DNA supercoiling and of how supercoiling influences gene expression and vice versa. Now they are contributing again by providing examples where changes in DNA supercoiling affect the expression of virulence traits that are important for infectious disease. Available examples encompass both the earliest stages of pathogen–host interactions and the more intimate relationships in which the bacteria invade and proliferate within host cells. A key insight concerns the link between the physiological state of the bacterium and the activity of DNA gyrase, with downstream effects on the expression of genes with promoters that sense changes in DNA supercoiling. Thus the expression of virulence traits by a pathogen can be interpreted partly as a response to its own changing physiology. Knowledge of the molecular connections between physiology, DNA topology and gene expression offers new opportunities to fight infection.     

Serum resistance in bvg-regulated mutants of Bordetella pertussis

Serum resistance, or resistance to killing by antibody dependent pathway of complement, in Bordetella pertussis is bvg-regulated and the Bordetella resistance to killing (brk) locus mediates much of the resistance. Here we examined whether other bvg-regulated proteins contribute to serum resistance. We found that neither pertussis toxin, adenylate cyclase toxin, filamentous hemagglutinin, dermonecrotic toxin, tracheal colonization factor, nor Vag8 mutants were sensitive to serum killing compared to the wild-type. Filamentous hemagglutinin has been reported to bind C4 binding protein, an inhibitor of complement, but this activity does not appear to contribute to serum resistance, as evidenced by the resistant phenotype of FHA mutants. Clinical isolates were serum resistant and wild-type strains possessing an additional copy of the brk locus were 2–5-fold more resistant to serum killing.