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Biophysics in the Understanding, Diagnosis, and Treatment of Infectious Diseases Poster Abstracts
86
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.