Pentobra: A novel antibiotic with potent antimicrobial activity against Propionibacterium acnes (TECH2P.901)

• Published in: The Journal of immunology (1950) 2015-05, Vol.194 (1_Supplement), p.206-206.11
• Main Authors: Agak, George, Schmidt, Nathan, Deshayes, Stephanie, Yu, Yang, Blacker, Alyssa, Champer, Jackson, Kao, Stephanie, Xian, Wujing, Kasko, Andrea, Kim, Jenny, Wong, Gerard
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.194.Supp.206.11

Although antibiotics are a common form of treatment against acne, the difficulties inherent to effective antimicrobial penetration in sebum and selective antimicrobial action in skin are recently compounded by increasing resistance of Propionibacterium acnes clinical isolates. To address these problems, we engineered Pentobra, a peptide-aminoglycoside molecule which has multiple mechanisms of antibacterial action, and investigated whether it can be a potential candidate for the treatment of acne. Pentobra combines the potent ribosomal activity of aminoglycosides with the bacteria-selective membrane-permeabilizing abilities of antimicrobial peptides. Pentobra demonstrated potent and selective killing of P. acnes, but not against human skin cells. In direct comparison, Pentobra demonstrated bactericidal activity and drastically outperformed free tobramycin (by 5-7 logs) against multiple P. acnes strains. Moreover, EM studies showed that Pentobra also had robust membrane activity, as treatment with Pentobra killed P. acnes cells. Pentobra may also have potential anti-inflammatory effects. Importantly, the killing activity was maintained in sebaceous environments as Pentobra was bactericidal against clinical isolates in microcomedone extracts isolated from human donors. Our work demonstrates that equipping aminoglycosides with selective membrane activity is a viable approach for developing new antibiotics against P. acnes that are effective in cutaneous environments.