ArticlePLoS biology2014
Mycobacterium tuberculosis Ser/Thr protein kinase B mediates an oxygen-dependent replication switch.
Article in PLoS biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
41 citing papers in PubMed, 73 citations in OpenAlex.
- Review
- Conserved mycobacterial sRNA B11 regulates lipooligosaccharide synthesis at posttranscriptional level inmLife · 2025Article
- Identifying Inhibitor Targets in Mycobacteria by Activity-Based Probe Profiling.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Polypharmacology-Driven Discovery and Design of Highly Selective, Dual and Multitargeting Inhibitors ofCurrent drug targets · 2024Review
- Chemical approaches to unraveling the biology of mycobacteria.Cell chemical biology · 2023Review
- Mycobacterial Regulatory Systems Involved in the Regulation of Gene Expression Under Respiration-Inhibitory Conditions.Journal of microbiology (Seoul, Korea) · 2023Review
- Chemoproteomic Approaches for Unraveling Prokaryotic Biology.Israel journal of chemistry · 2023Article
- Phosphorylation on PstP Regulates Cell Wall Metabolism and Antibiotic Tolerance in Mycobacterium smegmatis.Journal of bacteriology · 2021Article
- Modulation of the M. tuberculosis cell envelope between replicating and non-replicating persistent bacteria.Tuberculosis (Edinburgh, Scotland) · 2020Review
- Probing the Highly Disparate Dual Inhibitory Mechanisms of Novel Quinazoline Derivatives againstMolecules (Basel, Switzerland) · 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
- Protein kinases PknA and PknB independently and coordinately regulate essential Mycobacterium tuberculosis physiologies and antimicrobial susceptibility.PLoS pathogens · 2020Article
- Article
- The mycobacterial cell envelope - a moving target.Nature reviews. Microbiology · 2020Review
- Protein kinase B controls Mycobacterium tuberculosis growth via phosphorylation of the transcriptional regulator Lsr2 at threonine 112.Molecular microbiology · 2019Article
- Dual control of RegX3 transcriptional activity by SenX3 and PknB.The Journal of biological chemistry · 2019Article
- LipidII interaction with specific residues of Mycobacterium tuberculosis PknB extracytoplasmic domain governs its optimal activation.Nature communications · 2019Article
- In Silico Screen and Structural Analysis Identifies Bacterial Kinase Inhibitors which Act with β-Lactams To Inhibit Mycobacterial Growth.Molecular pharmaceutics · 2018Article
- GW779439X and Its Pyrazolopyridazine Derivatives Inhibit the Serine/Threonine Kinase Stk1 and Act As Antibiotic Adjuvants against β-Lactam-Resistant Staphylococcus aureus.ACS infectious diseases · 2018Article
- Incipient and Subclinical Tuberculosis: a Clinical Review of Early Stages and Progression of Infection.Clinical microbiology reviews · 2018Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The majority of Mycobacterium tuberculosis (Mtb) infections are clinically latent, characterized by drug tolerance and little or no bacterial replication. Low oxygen tension is a major host factor inducing bacteriostasis, but the molecular mechanisms driving oxygen-dependent replication are poorly understood. Here, we tested the role of serine/threonine phosphorylation in the Mtb response to altered oxygen status, using an in vitro model of latency (hypoxia) and reactivation (reaeration). Broad kinase inhibition compromised survival of Mtb in reaeration. Activity-based protein profiling and genetic mutation identified PknB as the kinase critical for surviving hypoxia. Mtb replication was highly sensitive to changes in PknB levels in aerated culture, and even more so in hypoxia. A mutant overexpressing PknB specifically in hypoxia showed a 10-fold loss in viability and gross morphological defects in low oxygen conditions. In contrast, chemically reducing PknB activity during hypoxia specifically compromised resumption of growth during reaeration. These data support a model in which PknB activity is reduced to achieve bacteriostasis, and elevated when replication resumes. Together, these data show that phosphosignaling controls replicative transitions associated with latency and reactivation, that PknB is a major regulator of these transitions, and that PknB could provide a highly vulnerable therapeutic target at every step of the Mtb life cycle-active disease, latency, and reactivation.
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Registered trials
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.