HlyC

HlyC is a cytosolic enzyme found in several Gram-negative bacteria, most notably Escherichia coli, where it participates in the post-translational activation of the pore-forming toxin hemolysin A (HlyA). It is encoded within the hemolysin gene cluster, commonly referred to as hlyCABD, and is required for the production of the fully active toxin.

Function and mechanism: HlyC acts as a fatty acyltransferase that transfers long-chain fatty acyl groups from acyl carrier protein (acyl-ACP) to specific lysine residues on HlyA. This results in an Nε-fatty acylated form of HlyA, a modification essential for the toxin’s proper folding, stability, and interaction with target cell membranes. The acylated HlyA is efficiently recognized by and secreted through the Type I secretion system, composed of HlyB, HlyD, and TolC, which transports the toxin directly from the cytoplasm to the extracellular space.

Genetic organization and regulation: The hlyCABD operon organizes the toxin gene (hlyA), the acyltransferase gene (hlyC), and the secretion apparatus genes. Regulation of the operon is coordinated with other virulence factors and can vary among strains and environmental conditions, reflecting the bacterium’s need to control toxin production.

Biological significance: HlyC-mediated modification is a key determinant of E. coli virulence in models of urinary tract infection and septicemia, as active HlyA contributes to host cell lysis and tissue damage. In strains lacking functional HlyC, HlyA remains largely non-toxic, underscoring the essential role of HlyC in producing the active hemolysin.

See also: Hemolysin A, Type I secretion system, HlyB, HlyD, TolC, acyltransferases, Escherichia coli virulence.