Bactericidal Disruption of Magnesium Metallostasis in Mycobacterium tuberculosis Is Counteracted by Mutations in the Metal Ion Transporter CorA.

ABSTRACT: A defining characteristic of treating tuberculosis is the need for prolonged administration of multiple drugs. This may be due in part to subpopulations of slowly replicating or nonreplicating Mycobacterium tuberculosis bacilli exhibiting phenotypic tolerance to most antibiotics in the standard treatment regimen. Confounding this problem is the increasing incidence of heritable multidrug-resistant M. tuberculosis A search for new antimycobacterial chemical scaffolds that can kill phenotypically drug-tolerant mycobacteria uncovered tricyclic 4-hydroxyquinolines and a barbituric acid derivative with mycobactericidal activity against both replicating and nonreplicating M. tuberculosis Both families of compounds depleted M. tuberculosis of intrabacterial magnesium.

SUBMITTER: Lopez Quezada L 

PROVIDER: S-EPMC6747715 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature