AphAAphB

AphA and AphB, collectively referred to as AphA/AphB in the literature, are transcriptional regulators found in Vibrio cholerae and related Vibrionaceae species. They occupy an early position in the bacterial virulence regulatory network and are central to controlling the expression of key virulence factors.

Function and regulatory role

AphA and AphB work together to activate the toxT gene, which encodes the master regulator ToxT. Once produced, ToxT directly activates the expression of virulence operons, including ctxAB, which encodes cholera toxin, and tcpA, a component of the toxin-coregulated pilus. This AphA/AphB–toxT axis is integrated with other regulatory systems such as the ToxR/ToxS regulon and the quorum-sensing network, allowing virulence gene expression to respond to environmental conditions and cell density.

Environmental sensing and expression

AphB is thought to function as a sensor-regulator that responds to environmental cues, while AphA complements this regulation to promote virulence gene expression under favorable conditions for infection. The activity of the AphA/AphB axis is modulated by signals associated with the host environment, and virulence gene expression is typically elevated at conditions that mimic the human intestinal milieu. At higher cell density, quorum-sensing regulators can counterbalance this activation to prevent unnecessary expression.

Clinical and research relevance

AphA/AphB are essential for understanding the regulation of V. cholerae virulence and pathogenesis. Disruption of either regulator reduces toxT activation and downstream virulence gene expression, attenuating virulence in experimental models. Ongoing research aims to clarify their precise molecular mechanisms and to explore them as potential targets for therapeutic intervention or prevention strategies.