Staphylococcus aureus leukocidin GH (LukGH (also known as LukAB))

Staphylococcus aureus leukocidin GH (LukGH), also known as LukAB, is a bi-component beta-barrel pore-forming cytotoxin secreted by the bacterium to evade host innate immunity. Composed of LukG (F-component, fast-migrating) and LukH (S-component, slow-migrating) subunits, each approximately 33 kDa, LukGH assembles into an octameric pore structure resembling alpha-hemolysin that inserts into target cell membranes, causing osmotic lysis and necrotic death primarily in phagocytic cells like human neutrophils, monocytes, and macrophages, as well as red blood cells to support bacterial nutrient acquisition. Unlike other S. aureus leukocidins that target G protein-coupled receptors, LukGH specifically binds the alpha-I domain of complement receptor 3 (CD11b/CD18, also called Mac-1 or CR3) on immune cells, with binding and subsequent oligomerization essential for cytotoxicity; this interaction shows strong species specificity, potently lysing human but not murine phagocytes due to differences in CD11b sequence. LukGH is one of up to five leukocidins produced by S. aureus (including PVL, HlgAB, HlgCB, LukED), contributing to virulence in infections such as skin/soft tissue abscesses, pneumonia, and sepsis by targeting and eliminating key immune effectors. It is expressed during human infections and considered the most potent S. aureus leukocidin in vitro and ex vivo, though limited activity in common animal models hampers pathogenesis studies. No approved drugs directly target LukGH, but structural insights into its receptor interaction offer potential for antitoxin development to combat antibiotic-resistant S. aureus strains.

Other names

leukocidin GHLukABLukG/LukH