a 1 Technische Universität Braunschweig, Institut für Mikrobiologie , Spielmannstr. 7, D-38106, Braunschweig, Germany ;
b 2 Türk-Alman Üniversitesi, Fen Fakültesi , Şahinkaya Cad. 86, 34820, Istanbul, Turkey.
Expert Opin Ther Targets. 2016;20(3):269-85. doi: 10.1517/14728222.2016.1090428. Epub 2015 Nov 13.
In recent years, Clostridium difficile has become the primary cause of antibiotic-associated diarrhea and pseudomembranous colitis, resulting in long and complicated hospital stays that represent a serious burden for patients as well as health care systems. Currently, conservative treatment of C. difficile infection (CDI) relies on the antibiotics vancomycin, metronidazole or fidaxomicin, or in case of multiple recurrences, fecal microbiota transplantation (FMT).
The fast-spreading, epidemic nature of this pathogen urgently necessitates the search for alternative treatment strategies as well as antibiotic targets. Accordingly, in this review, we highlight the recent findings regarding virulence associated traits of C. difficile, evaluate their potential as alternative drug targets, and present current efforts in designing inhibitory compounds, with the aim of pointing out possibilities for future treatment strategies.
Increased attention on systematic analysis of the virulence mechanisms of C. difficile has already led to the identification of several alternative drug targets. In the future, applying state of the art 'omics' and the development of novel infection models that mimic the human gut, a highly complex ecological niche, will unveil the genomic and metabolic plasticity of this pathogen and will certainly help dealing with future challenges.
近年来,艰难梭菌已成为抗生素相关性腹泻和伪膜性结肠炎的主要病因,导致患者住院时间延长且病情复杂,这给患者和医疗系统带来了严重负担。目前,艰难梭菌感染(CDI)的保守治疗依赖于抗生素万古霉素、甲硝唑或非达霉素,或者在多次复发的情况下,采用粪便微生物群移植(FMT)。
该病原体具有快速传播和流行的性质,因此迫切需要寻找替代治疗策略和抗生素靶标。因此,在这篇综述中,我们强调了艰难梭菌与毒力相关特征的最新发现,评估了它们作为替代药物靶标的潜力,并介绍了目前设计抑制化合物的努力,旨在指出未来治疗策略的可能性。
对艰难梭菌毒力机制的系统分析的关注度增加,已经导致了几个替代药物靶标的确定。未来,应用最先进的“组学”和开发模拟人类肠道这一高度复杂生态位的新型感染模型,将揭示该病原体的基因组和代谢可塑性,并肯定有助于应对未来的挑战。