ArticleEmerging microbes & infections2019
Housecleaning of pyrimidine nucleotide pool coordinates metabolic adaptation of nongrowing Mycobacterium tuberculosis.
Article in Emerging microbes & infections, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 13 citations in OpenAlex.
- Usnic Acid Derivatives as Inhibitors ofInternational journal of molecular sciences · 2026Article
- Targeting opportunities presented by the pyrimidine biosynthesis pathway in Mycobacterium tuberculosis: a brief review.Biochemical Society transactions · 2026Review
- Metabolic Changes in Zebrafish Larvae Infected withMetabolites · 2025Article
- Genome Sequences of the First Phages InfectingMicroorganisms · 2025Article
- Rifampicin drug resistance and host immunity in tuberculosis: more than meets the eye.Trends in immunology · 2023Review
- Metabolic Profiles of Clinical Isolates of Drug-Susceptible and Multidrug-ResistantInfection and drug resistance · 2023Article
- Structural analysis of the housecleaning nucleoside triphosphate pyrophosphohydrolase MazG fromFrontiers in microbiology · 2023Article
- HEmerging microbes & infections · 2022Article
- Phenotypic adaptation ofFrontiers in cellular and infection microbiology · 2022Review
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The ability of Mycobacterium tuberculosis (Mtb) to adopt a slowly growing or nongrowing state within the host plays a critical role for the bacilli to persist in the face of a prolonged multidrug therapy, establish latency and sustain chronic infection. In our previous study, we revealed that genome maintenance via MazG-mediated elimination of oxidized dCTP contributes to the antibiotic tolerance of nongrowing Mtb. Here, we provide evidence that housecleaning of pyrimidine nucleotide pool via MazG coordinates metabolic adaptation of Mtb to nongrowing state. We found that the ΔmazG mutant fails to maintain a nongrowing and metabolic quiescence state under dormancy models in vitro. To investigate bacterial metabolic changes during infection, we employed RNA-seq to compare the global transcriptional response of wild-type Mtb and the ΔmazG mutant after infection of macrophages. Pathway enrichment analyses of the differentially regulated genes indicate that the deletion of mazG in Mtb not only results in DNA instability, but also perturbs pyrimidine metabolism, iron and carbon source uptake, catabolism of propionate and TCA cycle. Moreover, these transcriptional signatures reflect anticipatory metabolism and regulatory activities observed during cell cycle re-entry in the ΔmazG mutant. Taken together, these results provide evidence that pyrimidine metabolism is a metabolic checkpoint during mycobacterial adaptation to nongrowing state.
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