LcrH

LcrH is a small cytosolic protein that functions as a chaperone within the type III secretion system (T3SS) of several Gram-negative bacteria, most notably Yersinia species. The name LcrH derives from its association with the low calcium response (Lcr) regulon that governs T3SS expression in these organisms. LcrH acts as a substrate-specific chaperone, binding to effector proteins destined for secretion and stabilizing them in the bacterial cytoplasm. This chaperone activity helps prevent premature aggregation of hydrophobic secretion substrates and facilitates their delivery to the secretion apparatus.

Within the T3SS landscape, LcrH forms complexes with its substrate proteins and interfaces with other secretion components to coordinate efficient secretion. Its function is tightly linked to virulence, as proper chaperoning is essential for the stability and translocation of virulence factors such as Yop proteins in Yersinia.

Genetically, lcrH is located within the T3SS gene cluster and its expression is coordinated with other virulence-associated genes. Environmental cues that activate the T3SS, such as host-like temperatures and calcium limitation, typically upregulate LcrH production in the context of a broader virulence response.

Structurally, LcrH is a relatively small acidic protein, commonly reported to be in the 14–20 kDa range, and is considered part of the class II family of chaperones associated with type III secretion substrates. Orthologous chaperones with similar roles are found in other bacteria that harbor T3SS systems.

Disruption of lcrH impairs secretion of Yersinia virulence factors and can attenuate virulence, highlighting its central role in pathogenicity and its relevance as a model for understanding chaperone-assisted substrate routing in bacterial secretion systems.