Importance of Glutamate Dehydrogenase (GDH) in Clostridium difficile Colonization In Vivo

Clostridium difficile is the principal cause of antibiotic-associated diarrhea. Major metabolic requirements for colonization and expansion of C. difficile after microbiota disturbance have not been fully determined. In this study, we show that glutamate utilization is important for C. difficile to establish itself in the animal gut. When the gluD gene, which codes for glutamate dehydrogenase (GDH), was disrupted, the mutant C. difficile was unable to colonize and cause disease in a hamster model. Further, from the complementation experiment it appears that extracellular GDH may be playing a role in promoting C. difficile colonization and disease progression. Quantification of free amino acids in the hamster gut during C. difficile infection showed that glutamate is among preferred amino acids utilized by C. difficile during its expansion. This study provides evidence of the importance of glutamate metabolism for C. difficile pathogenesis.艰难梭菌（Clostridium difficile）是抗生素相关性腹泻的首要致病原。微生物群扰动后，艰难梭菌定植与扩增所需的主要代谢需求尚未完全阐明。本研究证实，谷氨酸利用对于艰难梭菌在动物肠道内定殖至关重要。当编码谷氨酸脱氢酶（GDH）的gluD基因被敲除后，突变型艰难梭菌无法在仓鼠模型中定殖并引发疾病。此外，互补实验结果提示，胞外谷氨酸脱氢酶可能在促进艰难梭菌定殖与疾病进展中发挥作用。对艰难梭菌感染期间仓鼠肠道内游离氨基酸的定量分析显示，谷氨酸是艰难梭菌扩增过程中优先利用的氨基酸之一。本研究为谷氨酸代谢在艰难梭菌致病机制中的重要性提供了实验证据。