缩肽类化合物rakicidins体内外抗艰难梭菌活性研究

In vitro and in vivo activities of depsipeptide rakicidins against Clostridium difficile

目的研究海洋小单孢菌产生的缩肽类化合物rakicidins的体内外抗厌氧菌活性。方法微量肉汤稀释法测定rakicidins对厌氧菌的最小抑菌浓度(MIC);小鼠艰难梭菌感染相关性腹泻动物模型评价rakicidin Bx的治疗效果。结果 rakicidin A、B、B1及rakicidin Bx对艰难梭菌等革兰阳性厌氧菌有很强的抑制作用,MIC值0.125~0.25μg/m L。Rakicidin Bx对艰难梭菌感染的小鼠的保护作用虽略不及万古霉素和菲达霉素,但是停药后其与菲达霉素一样均未见复发。结论 Rakicidin Bx值得作为抗艰难梭菌感染的候选药物进行研发。

Objective To investigate the in vitro and in vivo anti-anaerobic bacteria activities of depsipeptide rakicidins from marine Micromonospora sp. Methods Broth microdilution methods were used to test the minimal inhibitory concentration （MIC） of rakicidins against Clostridium difficile and other anaerobicbacteria; the mouse model of C. difficile associated diarrhea was applied to assess the efficacy of rakicidin Bx. Results The MIC of rakicidin A, B, B 1 and Bx were approximately 0.125-0.25μg/mL against Gram positive anaerobicbacteria including C. difficile. In the mouse model of C. difficile infection （CDI）, rakicidin Bx showed slightly less protection than vancomycin or fidaxomicin. The recurrence of CDI was frequent for mice treated with vancomycin but not for mice receiving rakicidin Bx or fidaxomicin. Conclusion Rakicidin Bx could be a promising candidate for the CDI therapy.