GLOBAL REGULATORY MECHANISMS AFFECT VIRULENCE GENE-EXPRESSION IN BORDETELLA-PERTUSSIS

The influence was investigated of DNA gyrase-inhibiting drugs on the e xpression of various genes of Bordetella pertussis. We show that the p romoters of the virulence regulatory bvg locus and of several bvg-regu lated virulence factors, such as the fha, ptx, cya, fim2 and vrg6 loci are very sensitive to the action of novobiocin and coumermycin A, as reflected by transcriptional differences in gene expression. Inhibitio n of DNA gyrase by the drugs led to a strong decrease in transcription of these genes. Interestingly, one gene belonging to the bvg virulenc e regulon behaved differently: the promoter of the prn locus, coding f or the outer membrane protein pertactin, involved in bacterial adhesio n to eukaryotic cells, was induced after inhibition of DNA gyrase. The expression of other genes not belonging to the bvg regulon, such as t hose encoding porin (FOR) and superoxide dismutase (SodB), were not, o r only weakly, affected by the drugs. This demonstrates that with resp ect to drug-induced changes in DNA supercoiling there exist different types of promoters in B. pertussis. In an attempt to identify addition al regulatory mechanisms that may modulate virulence gene expression, we investigated the effect of various environmental stimuli on the sta bility of the bvg-regulated vrg6 and the bvg-independent sodB transcri pts. We found that some signals transduced via by the BvgS sensor prot ein, such as variations in the growth temperature or the presence of n icotinic acid, exerted a strong effect on the half life of these trans cripts, whereas another modulating agent, MgSO4, did not have any infl uence. These data suggest that the regulation of individual factors of the Bvg virulence regulon may be influenced by additional mechanisms, possibly involving differential effects on gene expression induced by changes in the DNA topology and the half-life of the respective mRNA.