AUTHOR=Samuels Amanda N. , Wang Erin R. , Harrison Gregory A. , Valenta Joy C. , Stallings Christina L. 

TITLE=Understanding the contribution of metabolism to Mycobacterium tuberculosis drug tolerance

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2022.958555

DOI=10.3389/fcimb.2022.958555

ISSN=2235-2988

ABSTRACT=<p>Treatment of <italic>Mycobacterium tuberculosis</italic> (<italic>Mtb)</italic> infections is particularly arduous. One challenge to effectively treating tuberculosis is that drug efficacy <italic>in vivo</italic> often fails to match drug efficacy <italic>in vitro.</italic> This is due to multiple reasons, including inadequate drug concentrations reaching <italic>Mtb</italic> at the site of infection and physiological changes of <italic>Mtb</italic> in response to host derived stresses that render the bacteria more tolerant to antibiotics. To more effectively and efficiently treat tuberculosis, it is necessary to better understand the physiologic state of <italic>Mtb</italic> that promotes drug tolerance in the host. Towards this end, multiple studies have converged on bacterial central carbon metabolism as a critical contributor to <italic>Mtb</italic> drug tolerance. In this review, we present the evidence that changes in central carbon metabolism can promote drug tolerance, depending on the environment surrounding <italic>Mtb</italic>. We posit that these metabolic pathways could be potential drug targets to stymie the development of drug tolerance and enhance the efficacy of current antimicrobial therapy.</p>