@article {10.7554/eLife.39169, article_type = {journal}, title = {\textit{Mycobacterium tuberculosis} induces decelerated bioenergetic metabolism in human macrophages}, author = {Cumming, Bridgette M and Addicott, Kelvin W and Adamson, John H and Steyn, Adrie JC}, editor = {Storz, Gisela and Kana, Bavesh D and Bald, Dirk and Jacobs, William R}, volume = 7, year = 2018, month = {nov}, pub_date = {2018-11-16}, pages = {e39169}, citation = {eLife 2018;7:e39169}, doi = {10.7554/eLife.39169}, url = {https://doi.org/10.7554/eLife.39169}, abstract = {How \textit{Mycobacterium tuberculosis} (\textit{Mtb}) rewires macrophage energy metabolism to facilitate survival is poorly characterized. Here, we used extracellular flux analysis to simultaneously measure the rates of glycolysis and respiration in real time. \textit{Mtb} infection induced a quiescent energy phenotype in human monocyte-derived macrophages and decelerated flux through glycolysis and the TCA cycle. In contrast, infection with the vaccine strain, \textit{M. bovis} BCG, or dead \textit{Mtb} induced glycolytic phenotypes with greater flux. Furthermore, \textit{Mtb} reduced the mitochondrial dependency on glucose and increased the mitochondrial dependency on fatty acids, shifting this dependency from endogenous fatty acids in uninfected cells to exogenous fatty acids in infected macrophages. We demonstrate how quantifiable bioenergetic parameters of the host can be used to accurately measure and track disease, which will enable rapid quantifiable assessment of drug and vaccine efficacy. Our findings uncover new paradigms for understanding the bioenergetic basis of host metabolic reprogramming by \textit{Mtb}.}, keywords = {\textit{Mycobacterium tuberculosis}, macrophages, bioenergetic metabolism, extracellular flux analysis, \textit{Mycobacterium bovis} BCG}, journal = {eLife}, issn = {2050-084X}, publisher = {eLife Sciences Publications, Ltd}, }