抗菌肽作为新型抗感染候选药物近年来受到密切关注。抗菌肽具有不易导致微生物耐药、杀菌时间快、不诱发微生物产生内毒素且可以中和内毒素因而不导致脓毒症的产生(传统抗生素可诱发脓毒症)等优点。
中国科学院昆明动物研究所赖仞研究员带领的课题组围绕抗菌肽的识别、发掘以及开发利用作了大量的工作,并建立中国抗菌肽分子资源库。痤疮是由痤疮丙酸杆菌等微生物导致的皮肤病,由于抗生素的不恰当使用,导致了大量的对传统抗生素耐药的痤疮丙酸杆菌的出现,因而急需新型的可以对抗耐药性痤疮丙酸杆菌的新型抗菌药物。最近该课题组发现,金环蛇来源的抗菌肽对痤疮丙酸杆菌具有显著的抗菌活性。他们利用小鼠构建了痤疮动物模型,研究了金环蛇来源的抗菌肽的体内抗痤疮效果。结果表明,该抗菌肽具有良好的体内痤疮治疗作用。作用机制研究表明,该抗菌肽通过抑制发炎因子的分泌和超氧阴离子的产生,从而抑制痤疮丙酸杆菌诱导的小鼠肉芽肿性炎。
该研究团队的部分研究结果近期发表于PLoS ONE(Cathelicidin-BF, a Snake Cathelicidin-Derived Antimicrobial Peptide, Could Be an Excellent Therapeutic Agent for Acne Vulgaris 2011,6:e22120)。该研究结果为该抗菌肽的进一步开发利用打下了重要基础。
原文出处:
PLoS ONE doi:10.1371/journal.pone.0022120.t001
Cathelicidin-BF, a Snake Cathelicidin-Derived Antimicrobial Peptide, Could Be an Excellent Therapeutic Agent for Acne Vulgaris
Yipeng Wang, Zhiye Zhang, Lingling Chen, Huijuan Guang, Zheng Li, Hailong Yang, Jianxu Li, Dewen You, Haining Yu, Ren Lai1
Cathelicidins are a family of antimicrobial peptides acting as multifunctional effector molecules in innate immunity. Cathelicidin-BF has been purified from the snake venoms of Bungarus fasciatus and it is the first identified cathelicidin antimicrobial peptide in reptiles. In this study, cathelicidin-BF was found exerting strong antibacterial activities against Propionibacterium acnes. Its minimal inhibitory concentration against two strains of P. acnes was 4.7 μg/ml. Cathelicidin-BF also effectively killed other microorganisms including Staphylococcus epidermidis, which was possible pathogen for acne vulgaris. Cathelicidin-BF significantly inhibited pro-inflammatory factors secretion in human monocytic cells and P. acnes-induced O2.? production of human HaCaT keratinocyte cells. Observed by scanning electron microscopy, the surfaces of the treated pathogens underwent obvious morphological changes compared with the untreated controls, suggesting that this antimicrobial peptide exerts its action by disrupting membranes of microorganisms. The efficacy of cathelicidin-BF gel topical administering was evaluated in experimental mice skin colonization model. In vivo anti-inflammatory effects of cathelicidin-BF were confirmed by relieving P. acnes-induced mice ear swelling and granulomatous inflammation. The anti-inflammatory effects combined with potent antimicrobial activities and O2.? production inhibition activities of cathelicidin-BF indicate its potential as a novel therapeutic option for acne vulgaris.