Institute of Basic Medical Sciences, National Cheng Kung University, 1 University Road, Tainan, 701, Taiwan.
Institute of Oral Medicine, National Cheng Kung University, 1 University Road, Tainan, 701, Taiwan.
Sci Rep. 2017 Aug 15;7(1):8124. doi: 10.1038/s41598-017-08387-y.
Clinical management of Clostridium difficile infection is still far from satisfactory as bacterial spores are resistant to many chemical agents and physical treatments. Certain types of nanoparticles have been demonstrated to exhibit anti-microbial efficacy even in multi-drug resistance bacteria. However, most of these studies failed to show biocompatibility to the mammalian host cells and no study has revealed in vivo efficacy in C. difficile infection animal models. The spores treated with 500 µg/mL FeO nanoparticles for 20 minutes, 64% of the spores were inhibited from transforming into vegetative cells, which was close to the results of the sodium hypochlorite-treated positive control. By cryo-electron micro-tomography, we demonstrated that FeO nanoparticles bind on spore surfaces and reduce the dipicolinic acid (DPA) released by the spores. In a C. difficile infection animal model, the inflammatory level triple decreased in mice with colonic C. difficile spores treated with FeO nanoparticles. Histopathological analysis showed a decreased intense neutrophil accumulation in the colon tissue of the FeO nanoparticle-treated mice. FeO nanoparticles, which had no influence on gut microbiota and apparent side effects in vivo, were efficacious inhibitors of C. difficile spore germination by attacking its surface and might become clinically feasible for prophylaxis and therapy.
艰难梭菌感染的临床管理仍然远不能令人满意，因为细菌孢子对许多化学试剂和物理处理具有抗性。某些类型的纳米粒子已被证明具有抗微生物功效，即使在多药耐药菌中也是如此。然而，这些研究大多数未能显示对哺乳动物宿主细胞的生物相容性，并且没有研究揭示在艰难梭菌感染动物模型中的体内功效。用 500μg/mL 的 FeO 纳米粒子处理 20 分钟后，有 64%的孢子被抑制转化为营养细胞，这与次氯酸钠处理的阳性对照结果相近。通过冷冻电子显微镜断层扫描，我们证明 FeO 纳米粒子结合在孢子表面，并减少孢子释放的二吡啶酸（DPA）。在艰难梭菌感染动物模型中，用 FeO 纳米粒子处理结肠艰难梭菌孢子的小鼠的炎症水平降低了三倍。组织病理学分析显示，用 FeO 纳米粒子处理的小鼠结肠组织中中性粒细胞的积聚明显减少。FeO 纳米粒子对肠道微生物群没有影响，并且在体内没有明显的副作用，它通过攻击孢子表面成为艰难梭菌孢子萌发的有效抑制剂，并且可能在预防和治疗方面具有临床可行性。
