HT61

**HT61** is a small quinolone-derived compound (molecular mass ~400 Da) with bactericidal activity against gram-positive bacteria, including methicillin-susceptible and methicillin-resistant *Staphylococcus aureus* (MSSA and MRSA), particularly effective against non-multiplying cells and biofilms. It acts as a membrane-active antimicrobial by partitioning into the negatively charged bacterial lipid bilayer due to its cationic charge, causing structural disruption, membrane depolarization, loss of integrity, ATP leakage, and eventual cell lysis. HT61 demonstrates synergy with aminoglycosides (e.g., neomycin, gentamicin, tobramycin) and antiseptics (e.g., chlorhexidine, mupirocin), enhancing their efficacy against *S. aureus* and tobramycin-resistant *Pseudomonas aeruginosa* strains in vitro, in biofilms, and in murine models of skin and pulmonary infections, though it shows limited direct activity alone against gram-negative bacteria.[1][2][3][5][6]