A team of investigators from the founding members of Mass General Brigham, Brigham and Women’s Hospital (BWH) and Massachusetts General Hospital (MGH), identified metabolic strategies used by Clostridium difficile To quickly colonize the gut. The findings identify ways to better prevent and treat the most common cause of antibiotic-associated diarrhea and health care acquired infections (HAIs). The team’s approach has implications for understanding broader aspects of microbial metabolism, including responses to antibiotics, and the production of important metabolites. The results are published in Chemical Nature Biology.
“Investigating real-time metabolism in microorganisms that only grow in environments that deficient in oxygen has been deemed impossible.” and Associate Professor of Pathology at Harvard Medical School. Here, we’ve shown it can be done to fight Jim hard Infection – and with findings that apply to clinical medicine.”
“Jim hard It is the leading cause of nosocomial infections and a major cause of antibiotic-associated diarrhea. Understanding metabolic mechanisms at the cellular level may be useful for infection prevention and treatment,” said co-senior author Leo L.
Jim hard It is a type of bacteria that is obligately anaerobic, which means that it does not reproduce in the presence of oxygen gas. Jim hard It causes inflammation by releasing toxins that allow the pathogen to obtain nutrients from damaged intestinal tissues. understand how Jim hard Metabolizing nutrients during gut colonization could direct new approaches to preventing and treating infections.
To complete their study, Bry and Cheng, faculty members of the recently formed Mass General Brigham Pathology Program, used a technique called high-resolution nuclear magnetic resonance (HRMAS NMR) spectroscopy to study metabolism in real time in living cells under anaerobic conditions. The team combined computational predictions to discover the metabolic shifts in Jim Saab As nutrient availability decreased, he then developed an approach to track the simultaneous flux of carbon and nitrogen through anaerobic metabolism. The researchers determined how Jim hard It initiates metabolism by fermenting amino acids before entering pathways for the fermentation of simple sugars such as glucose. They found that critical pathways converge at a point of metabolic integration to produce the amino acid alanine to efficiently drive bacterial growth.
The results of the study identified new targets for small molecule drugs to address Jim hard colonization and infection in the gut and providing a new approach for rapid identification of microbial metabolism for other applications, including antibiotic development and the production of economically and therapeutically important metabolites.
Study co-authors are Aidan Pavao, Brenta Gerinathan, Johan Peltier, Pamela Altamirano Silva, Bruno Dupuy, Isabella H. Muti, and Craig Malloy.
This work was supported by the National Institutes of Health, the BWH Precision Medicine Institute and Presidential Investigator Award, the MGH AA Martinos Center for Biomedical Imaging, and the Massachusetts Life Sciences Center.
