Biophysical Society Thematic Meeting - November 16-20, 2015

Biophysics in the Understanding, Diagnosis, and Treatment of Infectious Diseases Poster Abstracts

10-POS Board 10 Energy Metabolism of Mycobacterium Tuberculosis Infected Macrophages: Potential for Use as a Biomarker of Disease Progression and Severity Bridgette M Cumming 1 , Adrie JC Steyn 1,2 . 1 KwaZulu-Natal Research Institute for Tuberculosis and HIV, Durban, KwaZulu-Natal, South Africa, 2 University of Alabama at Birmingham, Birmingham, AL, USA. Bioenergetics has become central to understanding the pathology of human diseases such as neurodegeneration, diabetes, cancer and cardiovascular diseases. Recent studies have proposed the use of a single value termed the “Bioenergetic Health Index” (BHI) calculated from an oxidative phosphorylation profile to be used as a biomarker to assess patient health with prognostic and diagnostic value. From this perspective, our objective was to investigate if and how Mycobacterium tuberculosis ( Mtb ) infection modulates the energy metabolism of human macrophages derived from peripheral blood monocytes and the potential of monitoring bioenergetic metabolism as a biomarker of active infection. In order to differentiate Mtb infection from infections with other non-pathogenic mycobacterial species, M. bovis BCG infection (BCG), the strain used for vaccination, was investigated in parallel. We utilized extracellular flux analysis to measure oxygen consumption rate (OCR) as a measure of oxidative phosphorylation and extracellular acidification rate (ECAR) as a measure of glycolysis and the TCA cycle of the macrophages in real time and in a non-invasive manner. Mitochondrial modulating compounds revealed respiratory dysfunction in Mtb infected macrophages, in line with the greater dependency of Mtb infected macrophages on glycolysis as demonstrated by the greater sensitivity of these macrophages to 2-deoxyglucose that inhibits hexokinase II in glycolysis. Analysis of monocytes isolated from peripheral blood of healthy volunteers and a tuberculosis patient prior to treatment disclosed a significantly reduced spare respiratory capacity that reduced the calculated BHI. Future studies include monitoring the BHI of peripheral circulating monocytes isolated from tuberculosis patients prior to and during treatment to assess the value of BHI to monitor disease progression and response to treatment.

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