Importance of Glutamate Dehydrogenase (GDH) in Clostridium difficile Colonization In Vivo.
Importance of Glutamate Dehydrogenase (GDH) in Clostridium difficile Colonization In Vivo.
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DOI：
10.1371/journal.pone.0160107
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Govind R
中科院分区：
文献类型：
--
作者：
Girinathan BP;Braun S;Sirigireddy AR;Lopez JE;Govind R
艰难梭菌是抗生素相关性腹泻的主要原因。艰难梭菌在微生物区系紊乱后定植和扩张的主要代谢要求尚未完全确定。在这项研究中，我们表明谷氨酸的利用对于艰难梭菌在动物肠道中的建立是重要的。当编码谷氨酸脱氢酶(GDH)的Glud基因被破坏时，突变的艰难梭菌无法在仓鼠模型中定居并导致疾病。此外，从互补实验来看，胞外GDH可能在促进艰难梭菌定植和疾病进展方面发挥作用。艰难梭菌感染仓鼠肠道中游离氨基酸的定量检测表明，谷氨酸是艰难梭菌在扩张过程中优先利用的氨基酸之一。本研究为艰难梭菌致病过程中谷氨酸代谢的重要性提供了证据。
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.