Structural Refinement of teixobactin for treating complex Propionbacteriam acnes infection

Propionibacterium acnes, an aerotolerant anaerobic Gram-positive organism, is commonly known as a skin commensal due to its colonisation of the sebaceous glands and hair follicles. However, P. acnes can act as an opportunistic pathogen to cause invasive infections, particularly those associated with medical implants. P. acnes is the most frequently isolated pathogen in prosthetic shoulder joint infections, and is increasingly found in medical device-related cerebro- and cardiovascular infections. Until recently, P. acnes has been susceptible to a wide range of antibiotics. However, over the past 2 decades, resistance to metronidazole, macrolides, tetracycline and trimethoprim-sulfamethoxazole has been observed with increasing frequency. Hence, new classes of antibiotics are necessary to specifically combat medical device-associated infections caused by P. acnes.
Teixobactin is a recently discovered peptide antibiotic with potent antimicrobial activity against P. acnes. This project will entail the synthesis and microbiological evaluation of dual-action teixobactin analogues as potential antimicrobials for the treatment of P. acnes infections.