ArticleScientific reports2016
Establishing Virulence Associated Polyphosphate Kinase 2 as a drug target for Mycobacterium tuberculosis.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 49 citations in OpenAlex.
- Pharmacological inhibition of host pathways enhances macrophage killing of intracellular bacterial pathogens.Microbiology spectrum · 2026Article
- Mycobacterium tuberculosis overcomes phosphate starvation by extensively remodelling its lipidome with phosphorus-free lipids.Nature communications · 2025Article
- Platelet Polyphosphate Signals Through NFκB to Induce Myofibroblast Differentiation.Biomolecules · 2025Article
- Two endogenousProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Itaconate mechanism of action and dissimilation inProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Deciphering tuberculosis: lysosome-centric insights into pathogenesis and therapies.Frontiers in cellular and infection microbiology · 2025Review
- Mycobacterium tuberculosis strain with deletions in menT3 and menT4 is attenuated and confers protection in mice and guinea pigs.Nature communications · 2024Article
- Gene Regulatory Mechanism of Mycobacterium Tuberculosis during Dormancy.Current issues in molecular biology · 2024Review
- Polyphosphate kinase-1 regulates bacterial and host metabolic pathways involved in pathogenesis ofProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Tale of Twin Bifunctional Second Messenger (p)ppGpp Synthetases and Their Function in Mycobacteria.ACS omega · 2023Review
- A high-throughput dual system to screen polyphosphate kinase mutants for efficient ATP regeneration in L-theanine biocatalysis.Biotechnology for biofuels and bioproducts · 2023Article
- Progress Report: Antimicrobial Drug Discovery in the Resistance Era.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Polyphosphate Kinase 2 (PPK2) Enzymes: Structure, Function, and Roles in Bacterial Physiology and Virulence.International journal of molecular sciences · 2022Review
- Effects of Polyphosphate on Leukocyte Function.Progress in molecular and subcellular biology · 2022Review
- Inorganic polyphosphate in host and microbe biology.Trends in microbiology · 2021Review
- Semi-Automated High-Throughput Substrate Screening Assay for Nucleoside Kinases.International journal of molecular sciences · 2021Article
- Article
- Targeting theFrontiers in microbiology · 2021Review
- Insights on recent approaches in drug discovery strategies and untapped drug targets against drug resistance.Future journal of pharmaceutical sciences · 2021Review
- Broad-Spectrum Inhibitor of Bacterial Polyphosphate Homeostasis Attenuates Virulence Factors and Helps Reveal Novel Physiology ofFrontiers in microbiology · 2021Article
Corrections and comments
- Erratum issued
- Erratum issued
Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inorganic polyphosphate (PolyP) plays an essential role in microbial stress adaptation, virulence and drug tolerance. The genome of Mycobacterium tuberculosis encodes for two polyphosphate kinases (PPK-1, Rv2984 and PPK-2, Rv3232c) and polyphosphatases (ppx-1, Rv0496 and ppx-2, Rv1026) for maintenance of intracellular PolyP levels. Microbial polyphosphate kinases constitute a molecular mechanism, whereby microorganisms utilize PolyP as phosphate donor for synthesis of ATP. In the present study we have constructed ppk-2 mutant strain of M. tuberculosis and demonstrate that PPK-2 enzyme contributes to its ability to cause disease in guinea pigs. We observed that ppk-2 mutant strain infected guinea pigs had significantly reduced bacterial loads and tissue pathology in comparison to wild type infected guinea pigs at later stages of infection. We also report that in comparison to the wild type strain, ppk-2 mutant strain was more tolerant to isoniazid and impaired for survival in THP-1 macrophages. In the present study we have standardized a luciferase based assay system to identify chemical scaffolds that are non-cytotoxic and inhibit M. tuberculosis PPK-2 enzyme. To the best of our knowledge this is the first study demonstrating feasibility of high throughput screening to obtain small molecule PPK-2 inhibitors.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.