ArticlePloS one2011
The role of the novel exopolyphosphatase MT0516 in Mycobacterium tuberculosis drug tolerance and persistence.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 70 citations in OpenAlex.
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- Gallein and isoniazid act synergistically to attenuatebioRxiv : the preprint server for biology · 2024Article
- Gallein potentiates isoniazid's ability to suppressFrontiers in microbiology · 2024Article
- Cold atmospheric pressure plasma-antibiotic synergy inBiofilm · 2023Article
- Polyphosphate kinase 1 is involved in formation, the morphology and ultramicrostructure of biofilm ofHeliyon · 2023Article
- Phenotypic adaptation ofFrontiers in cellular and infection microbiology · 2022Review
- Genetic Determinants of Intrinsic Antibiotic Tolerance in Mycobacterium avium.Microbiology spectrum · 2021Article
- Targeting theFrontiers in microbiology · 2021Review
- Polyphosphate is an extracellular signal that can facilitate bacterial survival in eukaryotic cells.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Potential therapeutic approaches for a sleeping pathogen: tuberculosis a case for bioinorganic chemistry.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2020Review
- Article
- Antibiotic Treatment Shapes the Antigenic Environment During Chronic TB Infection, Offering Novel Targets for Therapeutic Vaccination.Frontiers in immunology · 2020Article
- Mechanisms of Antibiotic Tolerance inFrontiers in microbiology · 2020Review
- Tolerance and Persistence to Drugs: A Main Challenge in the Fight AgainstFrontiers in microbiology · 2020Review
- Phase variation inProceedings of the National Academy of Sciences of the United States of America · 2019Article
- Inorganic polyphosphate accumulation suppresses the dormancy response and virulence inThe Journal of biological chemistry · 2019Article
- Inhibiting the stringent response blocksScience advances · 2019Article
- Recombinant BCG Overexpressing phoP-phoR Confers Enhanced Protection against Tuberculosis.Molecular therapy : the journal of the American Society of Gene Therapy · 2018Article
- The stringent response and Mycobacterium tuberculosis pathogenesis.Pathogens and disease · 2018Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Inorganic polyphosphate (poly P) has been postulated to play a regulatory role in the transition to bacterial persistence. In bacteria, poly P balance in the cell is maintained by the hydrolysis activity of the exopolyphosphatase PPX. However, the Mycobacterium tuberculosis PPX has not been characterized previously. Here we show that recombinant MT0516 hydrolyzes poly P, and an MT0516-deficient M. tuberculosis mutant exhibits elevated intracellular levels of poly P and increased expression of the genes mprB, sigE, and rel relative to the isogenic wild-type strain, indicating poly P-mediated signaling. Deficiency of MT0516 resulted in decelerated growth during logarithmic-phase in axenic cultures, and tolerance to the cell wall-active drug isoniazid. The MT0516-deficient mutant showed a significant survival defect in activated human macrophages and reduced persistence in the lungs of guinea pigs. We conclude that exopolyphosphatase is required for long-term survival of M. tuberculosis in necrotic lung lesions.
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Registered trials
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