Staphylococcus aureus Panton-Valentine leukocidin S subunit (LukS-PV)

The Staphylococcus aureus Panton-Valentine leukocidin S subunit (LukS-PV) is the initial binding component of a potent bi-component pore-forming exotoxin (PVL) primarily associated with community-acquired methicillin-resistant S. aureus (CA-MRSA) [UniProt: P0A010]. LukS-PV specifically targets human neutrophils, monocytes, and macrophages by binding to the G-protein-coupled receptors C5aR1 and C5aR2 [PMID: 23603417]. Once bound, LukS-PV recruits the LukF-PV subunit to form a hetero-octameric pore that spans the host cell membrane, leading to osmotic imbalance, calcium influx, and eventually rapid cell death by lysis [PMID: 28414305]. This destruction of innate immune cells facilitates bacterial spread and contributes to the severe tissue necrosis observed in necrotizing pneumonia and deep skin infections [PMID: 15643011]. Therapeutic development focusing on LukS-PV includes monoclonal antibodies like ASN-1, part of the ASN100 complex, which aim to neutralize the toxin before it can compromise the immune system [NCT02940626]. Additionally, certain protein-synthesis-inhibiting antibiotics like linezolid and clindamycin are clinically prioritized because they suppress the production of the S-subunit even at sub-inhibitory concentrations [PMID: 17182705].

Other names

Panton-Valentine leukocidin S componentLukS-PVS-component of PVLLukSPanton-Valentine leucocidin chain S

Neutralization of the toxin's ability to bind to host cell receptors (C5aR1/C5aR2) or inhibition of toxin production at the ribosomal level to prevent assembly of the hetero-octameric pore.