PtxR directly binds promoter regions of virulence and metabolic genes. Key findings include:
PtxR enhances toxA expression by binding near the -35 region of its promoter, facilitating RNA polymerase recruitment . It also regulates gluconate metabolism by binding to P<sub>kgu</sub> and P<sub>gad</sub> .
PtxR’s activity is modulated by interactions with PtxS (a LacI-family repressor) and the metabolite 2-ketogluconate:
PtxS-PtxR complex: Forms a heterodimer with nanomolar affinity (ΔH = -27.3 kcal/mol) but dissociates in the presence of 2-ketogluconate .
Mechanistic outcomes:
PtxR integrates metabolic and virulence signals through cross-talk with other regulators:
Vfr dependency: Vfr binds the ptxR promoter (P2) and is essential for maximal toxA and lasB (metalloproteinase) expression .
Iron regulation: The ptxR promoter overlaps a PvdS (iron-starvation sigma factor) binding site, linking iron availability to virulence .
Carbon metabolism: PtxR-PtxS coordination ensures gluconate utilization is coupled to toxin production under host-relevant conditions .
Recombinant PtxR is produced via E. coli expression systems for functional studies:
KEGG: pae:PA2258
STRING: 208964.PA2258