Biophysical Society Thematic Meeting

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

Energy Metabolism in Mycobacterium Tuberculosis and the Infected Host Cell

Adrie Steyn

1,2

KwaZulu-Natal Research Institute for Tuberculosis and HIV, Durban, South Africa,

University of Alabama at Birmingham, Birmingham, AL, USA.

A major obstacle to the development of successful therapeutic intervention strategies for

tuberculosis (TB) is the lack of a mechanistic understanding of how M. tuberculosis (Mtb)

maintains a persistent, non-replicating state in humans for years, insensitive to antimycobacterial

drugs, to then unexpectedly resume growth and cause disease. Since numerous host factors can

affect Mtb physiology and energy metabolism, it is likely that the mechanisms used by the bacilli

to maintain energy balance during active disease are critical towards the outcome of disease.

What are the redox and bioenergetics states of infected host cells, and Mtb? How do we define

and measure it? Studies have shown that changes in bioenergetic metabolism accompany a wide

range of human diseases, and targeting shifts in bioenergetic metabolism may hold strong

therapeutic potential. My laboratory have used a combination of quantitative metabolomic,

transcriptomic, bioenergetic, EPR and mass spectrometric methods to examine mechanisms

whereby Mtb balances the cytoplasmic redox state and maintains bioenergetic homeostasis. I

will discuss approaches for characterizing the intracellular redox and bioenergetic status of Mtb

and the implications this knowledge have for studying the mode of action of antimycobacterial

drugs, and pathogenicity. Lastly, I will discuss how metabolic flux analysis can be exploited for

the non-invasive study of real-time Mtb bioenergetics.