platensimycin and Staphylococcal-Skin-Infections

Topics: Adamantane; Aminobenzoates; Anilides; Animals; Biofilms; Delayed-Action Preparations; Disease Models, Animal; Drug Liberation; Humans; Hydrogels; Male; Methicillin-Resistant Staphylococcus aureus; Mice; Microbial Sensitivity Tests; Nanoparticle Drug Delivery System; Polyamines; Staphylococcal Skin Infections; Wound Healing; Wound Infection

Staphylococcus aureus is one of the most common pathogens causing hospital-acquired and community-acquired infections. Methicillin-resistant S. aureus (MRSA)-formed biofilms in wounds are difficult to treat with conventional antibiotics. By targeting FabB/FabF of bacterial fatty acid synthases, platensimycin (PTM) was discovered to act as a promising natural antibiotic against MRSA infections. In this study, PTM and its previously synthesized sulfur-Michael derivative PTM-2t could reduce over 95% biofilm formation by S. aureus ATCC 29213 when used at 2 μg/mL in vitro. Topical application of ointments containing PTM or PTM-2t (2 × 4 mg/day/mouse) was successfully used to treat MRSA infections in a BABL/c mouse burn wound model. As a potential prodrug lead, PTM-2t showed improved in vivo efficacy in a mouse peritonitis model compared with PTM. Our study suggests that PTM and its analogue may be used topically or locally to treat bacterial infections. In addition, the use of prodrug strategies might be instrumental to improve the poor pharmacokinetic properties of PTM.

Topics: Adamantane; Aminobenzoates; Anilides; Animals; Anti-Bacterial Agents; Biofilms; Burns; Disease Models, Animal; Drug Resistance, Bacterial; Drug Stability; Fatty Acid Synthase, Type II; Fatty Acid Synthesis Inhibitors; Female; Methicillin-Resistant Staphylococcus aureus; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Microsomes; Peritonitis; Prodrugs; Staphylococcal Skin Infections; Sulfides; Treatment Outcome