Although
antibiotics are a common treatment for
acne, the difficulties inherent to effective antimicrobial penetration in sebum and selective antimicrobial action in the skin are compounded by increasing resistance of Propionibacterium acnes clinical isolates. To address these problems, we engineered
Pentobra, a
peptide-
aminoglycoside molecule that 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 vitro. In direct comparison,
Pentobra demonstrated bactericidal activity and drastically outperformed free
tobramycin (by 5-7 logs) against multiple P. acnes clinical strains. Moreover, electron microscopic studies showed that
Pentobra had robust membrane activity, as treatment with
Pentobra killed P. acnes cells and caused leakage of intracellular contents.
Pentobra may also have potential anti-inflammatory effects as demonstrated by suppression of some P. acnes-induced
chemokines. Importantly, the killing activity was maintained in sebaceous environments as
Pentobra was bactericidal against clinical isolates in comedones extracts isolated from human donors. Our work demonstrates that equipping
aminoglycosides with selective membrane activity is a viable approach for developing
antibiotics against P. acnes that are effective in cutaneous environments.