Novel Small Molecule Treatment for Staphylococcus Aureus SSTI Infections

SUMMARY

• Staphylococcus aureus infects 50,000 patients and kills 20,000 annually in the United States alone. With widespread antibiotic resistance, there is an urgent need for alternative mechanisms of targeting S. aureus infection. One way the pathogen mediates its virulence is by secreting the pore-forming cytotoxin α-hemolysin, which causes skin and soft tissue infections. This mechanism is not targeted by current therapeutic approaches.
• The inventors found that ADAM10 dismantles the structural framework of the epithelium, allowing α-hemolysin to exert its pathogenic activity. They therefore hypothesized that inhibiting ADAM10 would block α-hemolysin activity.
• The product is a method of using a novel group of small molecule inhibitors of ADAM10 that can be inhaled or topically delivered for the treatment of S. aureus infection. This therapeutic approach blocks bacterial infection, reduces disease severity, and promotes the healing process while avoiding common antibiotic resistance mechanisms.
• In mice challenged with S. Aureus infection, intraperitoneal injection of the ADAM 10 inhibitor increased mouse survival when the small molecule was administered therapeutically.