title: Metabolic profiling of lung granuloma in Mycobacterium tuberculosis infected guinea pigs: ex vivo 1H magic angle spinning NMR studies.
abstract: A crucial and distinctive feature of tuberculosis infection is that Mycobacterium tuberculosis (Mtb) resides in granulomatous lesion at various stages of disease development and necrosis, an aspect that is little understood. We used a novel approach, applying high resolution magic angle spinning nuclear magnetic resonance spectroscopy (HRMAS NMR) directly to infected tissues, allowing us to study the development of tuberculosis granulomas in guinea pigs in an untargeted manner. Significant up-regulation of lactate, alanine, acetate, glutamate, oxidized and the reduced form of glutathione, aspartate, creatine, phosphocholine, glycerophosphocholine, betaine, trimethylamine N-oxide, myo-inositol, scyllo-inositol, and dihydroxyacetone was clearly visualized and was identified as the infection progressed. Concomitantly, phosphatidylcholine was down-regulated. Principal component analysis of NMR data revealed clear group separation between infected and uninfected tissues. These metabolites are suggestive of utilization of alternate energy sources by the infiltrating cells that generate much of the metabolites in the increasingly necrotic and hypoxic developing granuloma through the glycolytic, pentose phosphate, and tricarboxylic acid pathways. The most relevant changes seen are, surprisingly, very similar to metabolic changes seen in cancer during tumor development.
authors: Department of Microbiology, Immunology and Pathology, Colorado State University, Campus Delivery 1682, Fort Collins, Colorado 80523-1682, United States.
authors: B S
authors: BS
authors: Somashekar
authors: Anita G
authors: AG
authors: Amin
authors: Christopher D
authors: CD
authors: Rithner
authors: JoLynn
authors: J
authors: Troudt
authors: Randall
authors: R
authors: Basaraba
authors: Angelo
authors: A
authors: Izzo
authors: Dean C
authors: DC
authors: Crick
authors: Delphi
authors: D
authors: Chatterjee
mesh_terms: D000818:Animals; D015687:Cell Hypoxia; D004195:Disease Models, Animal; D006099:Granuloma / Q000378:metabolism* / Q000382:microbiology*; D006168:Guinea Pigs; D006651:Histocytochemistry; D008066:Lipolysis; D008168:Lung / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D008171:Lung Diseases / Q000378:metabolism* / Q000382:microbiology*; D053858:Metabolic Networks and Pathways; D055442:Metabolome; D015999:Multivariate Analysis; D009169:Mycobacterium tuberculosis; D009336:Necrosis; D019906:Nuclear Magnetic Resonance, Biomolecular; D018384:Oxidative Stress; D025341:Principal Component Analysis; D014376:Tuberculosis / Q000378:metabolism*