Structural Refinement of teixobactin for treating complex Propionbacteriam acnes infection

痤疮丙酸杆菌是一种耐氧厌氧革兰氏阳性微生物，由于其定植于皮脂腺和毛囊，通常被称为皮肤共生体。然而，痤疮假单胞菌可以作为一种机会性的病原体，导致侵袭性感染，特别是与医疗植入物相关的感染。痤疮假单胞菌是人工肩关节感染中最常见的病原体，在与医疗器械相关的脑部和心血管感染中也越来越常见。直到最近，痤疮假单胞菌对多种抗生素都很敏感。然而，在过去的20年里，对甲硝唑、大环内酯类、四环素和甲氧苄氨嘧啶-磺胺甲恶唑的耐药性有所增加。因此，新的抗生素类别是必要的，以专门对抗由痤疮假单胞菌引起的医疗器械相关感染。替克生是一种新近发现的多肽抗生素，对痤疮假单胞菌具有很强的抗菌活性。该项目将需要合成和微生物学评价作为治疗痤疮假单胞菌感染的潜在抗菌剂的双作用替克生类似物。

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.