Mycobacterium Tuberculosis Metabolism and Host Interaction: Mysteries and Paradoxes

Abstract

Metabolism is a widely recognized facet of all host-pathogen interactions. Knowledge of its roles in pathogenesis, however, remains comparatively incomplete. Existing studies have emphasized metabolism as a cell autonomous property of pathogens used to fuel replication in a quantitative, rather than qualitatively specific, manner. For Mycobacterium tuberculosis, however, matters could not be more different. M. tuberculosis is a chronic facultative intracellular pathogen that resides in humans as its only known host. Within humans, M. tuberculosis resides chiefly within the macrophage phagosome, the cell type, and compartment most committed to its eradication. M. tuberculosis has thus evolved its metabolic network to both maintain and propagate its survival as a species within a single host. The specific ways in which its metabolic network serves these distinct, through interdependent, functions, however, remain incompletely defined. Here, we review existing knowledge of the M. tuberculosis-host interaction, highlighting the distinct phases of its natural life cycle and the diverse microenvironments encountered therein.

Acetate Dissimilation and Assimilation in Mycobacterium tuberculosis Depend on Carbon Availability

“…The detected levels of glucose or intermediates of the glycolysis were rather low, while free amino acids, organic acids, and lipid components accumulated during infection. These findings reflect the current concept about carbon sources utilized by M. tuberculosis in vitro and in vivo (47,48). The low level of glycolytic substrates indicates that acetate formation in M. tuberculosis might rely on other carbon sources than glucose.…”

A luciferase-based assay for rapid assessment of drug activity against Mycobacterium tuberculosis including monitoring of macrophage viability

“…Inside host cells, the bacterial metabolism alters to better resist the antimicrobial mechanisms of the cell, and this phenotypic shift has been linked to reduced susceptibility to drugs (Ehrt and Rhee, 2013;Schnappinger et al, 2003). Additionally, factors such as the level of intracellular penetration of the drugs as well as interaction with the immune defense mechanisms may affect the intracellular activity.…”

Glyoxylate detoxification is an essential function of malate synthase required for carbon assimilation in Mycobacterium tuberculosis

“…tuberculosis | metabolism | malate synthase | glyoxylate detoxification T he unusual evolution of Mycobacterium tuberculosis (Mtb) within humans as both host and reservoir has shaped its pathogenicity around adaptation of its carbon and energy metabolism to the diverse yet specific array of microenvironments encountered within human hosts (1). Current evidence indicates that Mtb can be found inside lipid-rich macrophages and in cavities, suggesting that these environments provide the pathogen with nutrients that facilitate persistence (2,3).…”