BvgAS

BvgAS is a two-component regulatory system found in Bordetella species, most notably Bordetella pertussis, that orchestrates the expression of virulence factors. It consists of BvgS, a sensor histidine kinase located in the inner membrane, and BvgA, a cytoplasmic response regulator. BvgS autophosphorylates in response to environmental cues and transfers the phosphate to BvgA. Phosphorylated BvgA binds targeted promoters to activate transcription of a virulence regulon, while in other states its activity is reduced, shifting the bacteria toward a less virulent phenotype.

The BvgA-regulated virulence genes include major adhesins and toxins such as pertussis toxin genes, adenylate cyclase toxin (CyaA), filamentous haemagglutinin (FhaB), pertactin (Prn), and other factors essential for colonization and immune evasion. BvgAS thereby coordinates a broad transcriptional program that enables Bordetella species to adapt between virulent and avirulent states in response to the environment.

Environmental signals modulate BvgAS activity. Conditions such as high concentrations of divalent cations (for example Mg2+ or MgSO4), presence of nicotinic acid, temperature shifts, and pH variations can shift the system toward a modulated state in which virulence gene expression is reduced. In host-like conditions, the BvgAS system tends to favor the Bvg+ state, promoting expression of virulence determinants during infection.

Structurally, BvgS contains periplasmic sensing domains and cytoplasmic kinase and receiver regions, whereas BvgA possesses a receiver domain and a DNA-binding output domain. The BvgAS regulon is central to Bordetella pathogenicity and is a target of study for understanding virulence regulation and for developing attenuated strains for vaccines and research tools.