Pourliotopoulou Evdokia, Karampatakis Theodoros, Kachrimanidou Melania
Department of Microbiology, Medical School, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece.
Microbiology Department, Papanikolaou General Hospital, 570 10 Thessaloniki, Greece.
Microorganisms. 2024 May 16;12(5):1004. doi: 10.3390/microorganisms12051004.
infection (CDI) is the leading cause of nosocomial antibiotic-associated diarrhea, and colitis, with increasing incidence and healthcare costs. Its pathogenesis is primarily driven by toxins produced by the bacterium , Toxin A (TcdA) and Toxin B (TcdB). Certain strains produce an additional toxin, the transferase (CDT), which further enhances the virulence and pathogenicity of . These toxins disrupt colonic epithelial barrier integrity, and induce inflammation and cellular damage, leading to CDI symptoms. Significant progress has been made in the past decade in elucidating the molecular mechanisms of TcdA, TcdB, and CDT, which provide insights into the management of CDI and the future development of novel treatment strategies based on anti-toxin therapies. While antibiotics are common treatments, high recurrence rates necessitate alternative therapies. Bezlotoxumab, targeting TcdB, is the only available anti-toxin, yet limitations persist, prompting ongoing research. This review highlights the current knowledge of the structure and mechanism of action of toxins and their role in disease. By comprehensively describing the toxin-mediated mechanisms, this review provides insights for the future development of novel treatment strategies and the management of CDI.
艰难梭菌感染（CDI）是医院获得性抗生素相关性腹泻和结肠炎的主要原因，其发病率和医疗成本不断增加。其发病机制主要由该细菌产生的毒素驱动，即毒素A（TcdA）和毒素B（TcdB）。某些菌株会产生另一种毒素，即二元毒素（CDT），这进一步增强了艰难梭菌的毒力和致病性。这些毒素破坏结肠上皮屏障的完整性，引发炎症和细胞损伤，导致CDI症状。在过去十年中，在阐明TcdA、TcdB和CDT的分子机制方面取得了重大进展，这为CDI的管理以及基于抗毒素疗法的新型治疗策略的未来发展提供了见解。虽然抗生素是常见的治疗方法，但高复发率需要替代疗法。靶向TcdB的贝佐妥单抗是唯一可用的抗毒素，但局限性仍然存在，这促使研究仍在继续。本综述强调了目前关于艰难梭菌毒素的结构和作用机制及其在疾病中的作用的知识。通过全面描述毒素介导的机制，本综述为新型治疗策略的未来发展和CDI的管理提供了见解。
