Ameliorating Staphylococcus aureus lung infections
Treatment failures for Staphylococcus aureus pneumonia are high despite antibiotic therapy. Heptameric toxin α-hemolysin (Hla) is a major pathogenicity factor of S. aureus due to its pore-forming and is a clinically validated target.
The researchers identified quinoxalinediones (QDS) small molecules that protect host cells by interacting with Hla near the phospholipid-binding site and preventing the formation of functional pores. QDS protects against the hallmarks of Hla-induced pathogenicity such as Ca2+ influx, cytotoxicity, hemolysis, and monolayer destruction.
They also demonstrate that QDS analog, H052, was active in mouse models of S. aureus lung infections, when administered prophylactically or therapeutically, either as monotherapy or when given in combination with the antibiotic linezolid.
Quinoxalinediones demonstrate how a large toxin can be inhibited by a small molecule with potency in vitro and in vivo.
https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(25)00089-7
https://sciencemission.com/quinoxalinediones-inhibit-a-hemolysin
