Metabolic Perspectives on Persistence

Abstract

SUMMARY Accumulating evidence has left little doubt about the importance of persistence or metabolism in the biology and chemotherapy of tuberculosis. However, knowledge of the intersection between these two factors has begun to emerge only recently. Here, we provide a focused review of metabolic characteristics associated with M. tuberculosis persistence. We focus on metabolism because it is the biochemical foundation of all physiologic processes and a distinguishing hallmark of M. tuberculosis’s physiology and pathogenicity. In addition, it serves as the chemical interface between host and pathogen. However, existing knowledge derives largely from physiologic contexts in which replication is the primary biochemical objective. The goal of this review is to reframe existing knowledge of M. tuberculosis metabolism in the context of persistence where quiescence is often a key distinguishing characteristic. Such a perspective may help guide ongoing efforts to develop more efficient cures and inform on novel strategies to break the cycle of transmission sustaining the pandemic.

Acetate metabolic requirement of avian pathogenic Escherichia coli promotes its intracellular proliferation within macrophage

“…The roles of this acetate assimilation system in APEC replication within macrophages were further determined. Recent evidences reveal that the intracellular pathogen can exploit its metabolic pathways to uptake host nutrient sources, aiming to enhance the active survival and proliferation in host intracellular compartments [4, 6, 7, 55]. Lactate dehydrogenases (LDHs) is an important survival factor of Neisseria gonorrhoeae to uptake host-derived lactate, which is the critical carbon source for survival/replication of N. gonorrhoeae in phagocytic or epithelial cells [56].…”

Evolution of Drug-Resistant Mycobacterium tuberculosis Strains and Their Adaptation to the Human Lung Environment

“…This reversible phenomenon is usually induced by external stresses such as hypoxia or drug treatment, among others factors ( Vilcheze and Jacobs, 2019 ), and is associated with a nonreplicating status of the bacilli. Several M.tb factors and metabolic traits are linked to M.tb persistence ( Keren et al, 2011 ; Lee et al, 2019 ), although the evidence suggests that persistence consists of an array of heterogenous physiological states and mechanisms ( Hartman et al, 2017 ). Mechanisms of M.tb persistence are still being elucidated; however, different bacterial metabolic status during early stages of the infection might explain why some M.tb subpopulations can become phenotypically drug-resistant.…”

Drug-Tolerant Mycobacterium tuberculosis Adopt Different Survival Strategies in Alveolar Macrophages of Patients with Pulmonary Tuberculosis

“…It is assumed that persistent Mtb constitutes a reservoir of slow-growing or growtharrested bacteria, in which many antibiotic target sites are inactive, thereby explaining the ineffectiveness of bactericidal antibiotics [20][21][22]. Several observations correlate the physiological state of the pathogen with dormancy, which is usually associated with the inability of Mtb to grow on solid media, its reduced metabolic and growth rates, resulting from alteration of gene expression, and tolerance to antibiotics owing to lack of replication and cell wall remodeling [23][24][25].…”