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...

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Bibliographic Details
Published in:PloS one 2016-07, Vol.11 (7), p.e0160107-e0160107
Main Authors: Girinathan, Brintha Parasumanna, Braun, Sterling, Sirigireddy, Apoorva Reddy, Lopez, Jose Espinola, Govind, Revathi
Format: Article
Language:English
Subjects:
Amino acids
Ammonia
Analysis
Animals
Antibiotics
Bacillus subtilis
Bacteria
Biology
Biology and Life Sciences
Care and treatment
Cloning
Clostridioides difficile - enzymology
Clostridioides difficile - growth & development
Clostridium difficile
Clostridium perfringens
Colonization
Complementation
Complications and side effects
Cricetinae
Dehydrogenase
Dehydrogenases
Deoxyribonucleic acid
Development and progression
Diarrhea
DNA
Drug resistance
Enzymes
Glutamate dehydrogenase
Glutamate Dehydrogenase - metabolism
Health aspects
Infections
Medicine and Health Sciences
Metabolism
Microbiota
Pathogenesis
Physiological aspects
Plasmids
Research and Analysis Methods
Rodents
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0160107