Leukocidin GH (LukGH) (LukGH)

Leukocidin GH (LukGH), also known as LukAB, is a potent bi-component pore-forming toxin secreted by Staphylococcus aureus that plays a critical role in bacterial pathogenesis by targeting and killing human phagocytes (Source 1, 9). It is unique among staphylococcal leukocidins because its subunits, LukG and LukH, form a stable heterodimer in solution before engaging with the host cell (Source 4, 6). The toxin specifically binds to the CD11b subunit of the Mac-1 integrin (CD11b/CD18) and requires the hydrogen voltage-gated channel 1 (HVCN1) for full cytotoxic activity (Source 1, 18). Upon binding, LukGH oligomerizes into an octameric beta-barrel pore that penetrates the plasma membrane, leading to rapid osmotic lysis and the release of pro-inflammatory mediators (Source 10, 20). As a core genome-encoded virulence factor present in nearly all S. aureus isolates, LukGH is a major target for the development of neutralizing monoclonal antibodies and vaccines to combat invasive infections, including those caused by MRSA (Source 2, 12). Therapeutic strategies such as intravenous immunoglobulin (IVIg) have been shown to contain functional neutralizing antibodies against this toxin (Source 8, 11). The high species specificity of LukGH, which is inactive against murine cells, presents a significant challenge for preclinical drug development in standard mouse models (Source 10, 20). Neutralizing this toxin aims to preserve the host's innate immune response and reduce the severity of necrotizing infections (Source 3, 6).

Other names

LukABLeukocidin A/BLeukocidin GHLukA/LukBLukG/LukH

Binds to CD11b and HVCN1 receptors on leukocytes, followed by oligomerization into an octameric beta-barrel pore that causes osmotic lysis.