Understanding the contribution of metabolism to Mycobacterium tuberculosis drug tolerance.
Understanding the contribution of metabolism to Mycobacterium tuberculosis drug tolerance.
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DOI：
10.3389/fcimb.2022.958555
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发表时间：
2022
影响因子：
5.7
通讯作者：
中科院分区：
文献类型：
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治疗结核分枝杆菌（Mtb）感染尤其困难。有效治疗结核病的一个挑战是体内药物疗效往往不能与体外药物疗效相匹配。这是由多种原因造成的，包括到达结核分枝杆菌感染部位的药物浓度不足，以及结核分枝杆菌对宿主产生的应激反应的生理变化，使细菌对抗生素更具耐受性。为了更有效和高效地治疗结核病，有必要更好地了解促进宿主耐药的Mtb生理状态。为此，多项研究都集中在细菌中心碳代谢是结核分枝杆菌耐药的关键因素。在这篇综述中，我们提供的证据表明，中枢碳代谢的变化可以促进耐药，这取决于结核分枝杆菌周围的环境。我们假设这些代谢途径可能是潜在的药物靶点，以阻止药物耐受性的发展，提高当前抗菌治疗的疗效。
Treatment of Mycobacterium tuberculosis (Mtb) infections is particularly arduous. One challenge to effectively treating tuberculosis is that drug efficacy in vivo often fails to match drug efficacy in vitro. This is due to multiple reasons, including inadequate drug concentrations reaching Mtb at the site of infection and physiological changes of Mtb 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 Mtb that promotes drug tolerance in the host. Towards this end, multiple studies have converged on bacterial central carbon metabolism as a critical contributor to Mtb drug tolerance. In this review, we present the evidence that changes in central carbon metabolism can promote drug tolerance, depending on the environment surrounding Mtb. 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.