Division of Gastroenterology and Hepatology, Department of Medicine, Rochester, Minnesota.
Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Rochester, Minnesota.
Gastroenterology. 2021 Feb;160(3):941-945.e8. doi: 10.1053/j.gastro.2020.10.046. Epub 2020 Nov 14.
The increasing incidence of primary and recurring Clostridioides difficile infections (CDI), which evade current treatment strategies, reflects the changing biology of C difficile. Here, we describe a putative plasmid-mediated mechanism potentially driving decreased sensitivity of C difficile to vancomycin treatment. We identified a broad host range transferable plasmid in a C difficile strain associated with lack of adequate response to vancomycin treatment. The transfer of this plasmid to a vancomycin-susceptible C difficile isolate decreased its susceptibility to vancomycin in vitro and resulted in more severe disease in a humanized mouse model. Our findings suggest plasmid acquisition in the gastrointestinal tract to be a possible mechanism underlying vancomycin treatment failure in patients with CDI, but further work is needed to characterize the mechanism by which plasmid genes determine vancomycin susceptibility in C difficile.
艰难梭菌（Clostridioides difficile）感染（CDI）的发病率不断上升，目前的治疗策略对此也无能为力，这反映出艰难梭菌的生物学特性正在发生变化。在这里，我们描述了一种可能的质粒介导机制，该机制可能导致艰难梭菌对万古霉素治疗的敏感性降低。我们在一株与万古霉素治疗反应不足相关的艰难梭菌菌株中发现了一种广泛宿主范围的可转移质粒。该质粒转移到一株对万古霉素敏感的艰难梭菌分离株中，使其对万古霉素的敏感性降低，并在人源化小鼠模型中导致更严重的疾病。我们的研究结果表明，胃肠道中质粒的获得可能是 CDI 患者万古霉素治疗失败的一个潜在机制，但需要进一步研究来阐明质粒基因如何决定艰难梭菌对万古霉素的敏感性。
