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Abstract #3260

A Small Volatile Bacterial Molecule Triggers Oxidative Stress, Apoptosis Insulin Resistance and Concurs with Mitochondrial Dysfunction in Murine Skeletal Muscle

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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Keywords

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