Gamma-hemolysin component C (HlgC)

Gamma-hemolysin component C (HlgC) is a secreted protein produced by Staphylococcus aureus that serves as the S-component (slow-eluted) of a bicomponent pore-forming toxin (UniProt: P0A075). It functions by pairing with the F-component (fast-eluted), Gamma-hemolysin component B (HlgB), to form an octameric pore in the plasma membranes of host cells, specifically targeting human polymorphonuclear leukocytes, monocytes, and macrophages (PubMed: 25135834). This pore formation leads to the rapid efflux of ions, osmotic instability, and eventual cytolysis, which allows the bacteria to evade the host immune system and cause extensive tissue damage (PubMed: 23530043). HlgC is recognized as a major virulence factor in various staphylococcal pathologies, including necrotizing pneumonia and severe skin infections (PubMed: 26951486). From a therapeutic perspective, HlgC has been targeted by neutralizing monoclonal antibodies like those in the ASN100 cocktail (ASN-1), which aim to prevent the toxin from binding to its host receptors or assembling into a functional pore (ClinicalTrials.gov: NCT02940626). Although some clinical trials for anti-toxin therapies have encountered difficulties in achieving primary endpoints, HlgC remains a high-priority target for developing adjunctive treatments against multi-drug resistant S. aureus.

Other names

HlgCGamma-hemolysin subunit CLeukocidin HlgC componentStaphylococcal gamma-hemolysin CGamma-Hl component C

Neutralization of the toxin component to prevent the assembly of the octameric pore-forming complex on host cell membranes.