Discovery of plants and fungi with antibacterial activity against Propionibacterium acnes

Acne vulgaris is a common skin disorder that affects >85% of teenagers. Propionibacterium acnes is implicated in its pathogenesis, and like many other bacteria, is subject to emerging trends in antibiotic resistance. Novel therapies are in high demand. The aim of this study was to identify new leads for future pre-clinical development from herbal skin remedies used in Italy. We screened a unique natural product library composed of extracts from medicinal and randomly collected plants and fungi from the Mediterranean for growth-inhibitory and anti-biofilm activity in P. acnes. Evaluation of 157 extracts from 10 fungi and 58 plants led to the identification of crude extracts from seven species exhibiting growth inhibitory activity (MICs from 64-256 μg mL-1) and one with biofilm eradication activity (MBEC of 256 μg mL-1). None of these species, with the exception of Sweet Chestnut, have ever been reported for activity against P. acnes. All active extracts were examined for cytotoxicity against an immortalized line of human keratinocytes (HaCaT), and while most were non-toxic, one fungal species was toxic at the same concentration required for its anti-acne activity (IC50=256 μg mL-1). Comparison of these extracts to natural product standards by HPLC revealed the presence of chlorogenic acid, p-coumaric acid, ellagic acid, gallic acid and tannic acid. The compound responsible for toxicity in the bioactive fungal sample was determined by LC-FTMS to be polyporic acid. Species used in the traditional medicine for skin infections and inflammations exhibited significantly greater (p<0.05) growth inhibitory activity than those with no reported topical application, suggesting that herbal remedies remain an untapped source for discovery efforts aimed at development of new therapeutics and cosmeceuticals for acne.