Panton–Valentine leukocidin S component (LukS-PV)

Panton–Valentine leukocidin (PVL) is a potent bicomponent pore-forming cytotoxin produced by certain strains of Staphylococcus aureus, most notably community-associated methicillin-resistant S. aureus (CA-MRSA) (UniProt P0A010). The S component (LukS-PV) serves as the initial binding subunit that recognizes and attaches to specific G protein-coupled receptors, primarily the C5a anaphylatoxin receptors C5aR1 and C5aR2, on the surface of human neutrophils and macrophages (Spaan et al., 2013). Upon binding, LukS-PV recruits the F component (LukF-PV) to form a hetero-octameric prepore that subsequently inserts into the host cell membrane to create a functional pore. This process leads to osmotic imbalance, rapid cell lysis, and the release of pro-inflammatory cytokines, which contributes to the severe tissue necrosis characteristic of PVL-associated diseases. Clinically, LukS-PV is a major virulence factor linked to aggressive skin and soft tissue infections and life-threatening necrotizing pneumonia (PubMed: 17443036). Therapeutic strategies targeting LukS-PV include the development of monoclonal antibodies like ASN100, which aim to neutralize the toxin and prevent its interaction with host immune cells. Furthermore, certain antibiotics such as clindamycin and linezolid are utilized in clinical practice specifically for their ability to inhibit the production of this toxin, thereby mitigating the inflammatory damage during severe staphylococcal infections.

Other names

LukS-PVPanton-Valentine leukocidin subunit SLeukocidin S subunitS-component of PVLStaphylococcal LukS-PV

Neutralization of the LukS-PV subunit by monoclonal antibodies prevents its binding to host cell receptors (C5aR1/C5aR2), thereby inhibiting the recruitment of LukF-PV and the subsequent assembly of the hetero-octameric pore that causes cell lysis. Additionally, protein synthesis inhibitors like clindamycin and linezolid suppress the translation of the toxin at the ribosomal level.