Valeria Righi1, 2, Caterina Constantinou3, Nikolaos Psychogios, 24, Julie Wilhelmy5, Michael Mindrinos5, Laurence G. Rahme3, Aria A. Tzika, 24
1NMR Surgical Laboratory, Department of Surgery , Massachusetts General Hospital and Shriners Burns Institute, Harvard Medical School, Boston , MA, United States; 2Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States; 3Molecular Surgery Laboratory, Department of Surgery, Massachusetts General Hospital and Shriners Burn Institute, Harvard Medical School, Boston, MA, United States; 4NMR Surgical Laboratory, Department of Surgery, Massachusetts General Hospital and Shriners Burns Institute, Harvard Medical School, Boston, MA, United States; 5Department of Biochemistry, Stanford University School of Medicine, Stanford, CA, United States
We hypothesized that a volatile aromatic molecule, 2-amino acetophenone (2-AA), produced by the human pathogen Pseudomonas aeruginosa endangers the host. We used a novel high-resolution magic-angle-spinning (HRMAS), proton nuclear magnetic resonance (NMR) metabolomics method, in vivo 31P NMR and a whole-genome expression approach to identify the effects of 2AA on murine skeletal muscle. We observed oxidative stress apoptosis and insulin resistance status associated with a mitochondrial dysfunction molecular signature in skeletal muscle following 2-AA treatment, which may be linked to 2-AAs ability to promote bacterial phenotypic changes associated with chronic inflammatory disease and infection.
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