ExsD

ExsD is a regulatory protein found in several Gram-negative bacteria, most notably Pseudomonas aeruginosa, where it functions as a negative regulator of Type III secretion system (T3SS) gene expression. It achieves this in part by directly binding to the transcriptional activator ExsA, thereby repressing ExsA-dependent transcription of T3SS operons.

ExsD is part of the ExsACDE regulatory module that controls T3SS expression. Under non-inducing conditions, ExsE binds ExsC, preventing ExsC from neutralizing ExsD. ExsD remains free to bind ExsA and repress transcription of T3SS genes. Upon secretion system induction, ExsE is secreted, releasing ExsC to bind ExsD; this sequestration disrupts the ExsA–ExsD interaction, allowing ExsA to activate transcription of T3SS genes.

Biochemical and genetic studies have shown direct interactions between ExsD and ExsA, as well as between ExsD and ExsC, supporting their roles in the regulatory cascade. Genetic disruption of exsD often leads to constitutive expression of T3SS components, underscoring ExsD’s role as a negative regulator in controlling virulence-associated gene expression.

Structure and regulation of ExsD reflect its function within the ExsACDE network. While detailed structural information is limited in this overview, the protein is characterized by its cytosolic localization and its capacity to form regulatory interactions with ExsA and ExsC, modulated by the secretion-dependent status of ExsE.

Relevance: The T3SS is a major virulence determinant in P. aeruginosa and related bacteria. By modulating ExsA activity, ExsD influences the timing and level of T3SS expression, making it a focal point for research into anti-virulence strategies and bacterial pathogenesis.