ExsE

ExsE is a small secreted regulatory protein associated with the type III secretion system (T3SS) in several Gram-negative bacteria, most prominently Pseudomonas aeruginosa and Vibrio species such as Vibrio cholerae. It forms part of a regulatory cascade that also includes ExsA, the transcriptional activator, and the regulatory proteins ExsD (anti-activator) and ExsC (anti-anti-activator).

In the cytoplasm, ExsE binds ExsC, preventing ExsC from inhibiting ExsD. This keeps ExsA repressed and prevents transcription of T3SS genes. When the T3SS is active and ExsE is secreted through the secretion apparatus, its cytosolic concentration drops. Freed ExsC can then bind ExsD, which releases ExsA from inhibition. Activated ExsA promotes transcription of T3SS structural components and effector proteins, linking secretion activity to gene expression.

Genetic organization and regulation of ExsE can vary among species but it is typically part of the exsC-exsD-exsA-exsE regulatory cluster and is coordinated with environmental cues such as host contact or conditions that stimulate secretion. The ExsE-centered module thus serves as a sensory mechanism that couples the assembly of the secretion system to the expression of its components, ensuring a coordinated virulence program.

Clinical and research relevance: Because the T3SS is a key virulence factor in many pathogens, ExsE and the ExsC–ExsD–ExsA regulatory axis are of interest for understanding bacterial pathogenesis and for exploring potential therapeutic targets aimed at disarming rather than killing bacteria. The ExsE system has been studied most extensively in Pseudomonas aeruginosa and related species.