Sequential activation and environmental regulation of virulence genes in Bordetella pertussis.

Abstract

Bacterial pathogens undergo profound physiological changes when they infect their host and require coordinated regulation of gene expression in response to the stress encountered during infection. In Bordetella pertussis, the human pathogen which causes whooping cough, virulence factors are synthesized in response to environmental signals under the control of the bvg regulatory locus. Here we demonstrate that the bvg locus is responsible for two events of gene activation. In the first step the bvg locus transactivates its own autoregulated promoter (P1) and the promoter of the adherence factor filamentous haemagglutinin (PFHA).The second step occurs several hours later and consists of the transactivation of adenylate cyclase and pertussis toxin genes. We provide evidence that the second step of transactivation requires overexpression of regulatory proteins. Our results imply that bacterial adhesion and tissue colonization -intoxication are two separate steps at the molecular level.

BvgAS is sufficient for activation of the Bordetella pertussis ptx locus in Escherichia coli

“…Our data support a model proposed by Scarlato et al in which the fhaB and ptxA promoters have different sensitivities to BvgA (44). In this model, low levels of activated BvgA permit fhaB but not ptxA expression.…”

“…ptxA and cya transcripts are not detected until hours after a switch from modulating to nonmodulating conditions, in contrast to fhaB and bvg transcripts, which are observed within a few minutes (44). This observation is consistent with results indicating that ptxA and cya are more sensitive to modulation than fhaB and bvg (46a, 48).…”

“…For maximal ptxA expression, larger amounts of activated BvgA are predicted to be necessary. Higher levels of BvgA have been correlated with activation of ptxA in B. pertussis, and it has been suggested that ptxA expression requires a threshold level of BvgA (44). Our results have defined a system which reproduces activation of ptxA by bvg and will now permit further analysis of conditions The whole-cell lysates described above were subjected to Western blot analysis using monoclonal anti-BvgS and monoclonal anti-BvgA antibodies.…”

“…However, fhaB and ptxA have different temporal patterns of expression following a shift from modulating to nonmodulating conditions (44) and distinct requirements for expression in E. coli (33). This has led to speculation that the bvg virulence control system may have a downstream activator that participates in ptxA expression, much like the ToxRS-ToxT regulatory system of Vibrio cholerae (13).…”

The Bordetella pertussis model of exquisite gene control by the global transcription factor BvgA

“…Virulence genes whose products are presumably involved early in pathogenesis -such as surface-expressed adhesin proteins and BvgA itself -are activated almost immediately upon a shift to permissive growth conditions (37 u C) (Scarlato et al, 1991) (Fig. 1c).…”