Evidence map›Paper›PMID 31562654›Full record

ArticleMolecular microbiology2019

Protein kinase B controls Mycobacterium tuberculosis growth via phosphorylation of the transcriptional regulator Lsr2 at threonine 112.

Kawther Alqaseer, Obolbek Turapov, Philippe Barthe, Heena Jagatia, Angélique De Visch, Christian Roumestand, Malgorzata Wegrzyn, Iona L Bartek, Martin I Voskuil, Helen M O'Hare and 6 more

Open access · hybridAbstract read
In one paragraph

Article in Molecular microbiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.9field-weighted citation impact, top 15% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 24 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Transcriptional regulation and drug resistance inFrontiers in cellular and infection microbiology · 2022
    Review
  10. Elimination of PknL and MSMEG_4242 inCell surface (Amsterdam, Netherlands) · 2021
    Article
  11. Article
  12. Article
  13. Article
  14. Alterations in the Cell Wall ofFrontiers in microbiology · 2020
    Article
  15. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 6 institutions in 4 countries.

Kawther AlqaseerLeicester Tuberculosis Research Group, Department of Respiratory Sciences, University of Leicester, Leicester, LE2 9HN, UK.
Obolbek TurapovLeicester Tuberculosis Research Group, Department of Respiratory Sciences, University of Leicester, Leicester, LE2 9HN, UK.
Philippe BartheCentre de Biochimie Structurale, CNRS, INSERM, University of Montpellier, 34090, Montpellier, France.
Heena JagatiaWellcome Trust Brighton and Sussex Centre for Global Health Research, Brighton and Sussex Medical School, University of Sussex, Brighton, BN1 9PX, UK.
Angélique De VischCentre de Biochimie Structurale, CNRS, INSERM, University of Montpellier, 34090, Montpellier, France.
Christian RoumestandCentre de Biochimie Structurale, CNRS, INSERM, University of Montpellier, 34090, Montpellier, France.
Malgorzata WegrzynCore Biotechnology Services, University of Leicester, University Road, Leicester, LE1 7RH, UK.
Iona L BartekDepartment of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO, 80045, USA.
Martin I VoskuilDepartment of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO, 80045, USA.
Helen M O'HareLeicester Tuberculosis Research Group, Department of Respiratory Sciences, University of Leicester, Leicester, LE2 9HN, UK.
Paul AjuhGemini Biosciences Ltd, Liverpool Science Park, Liverpool, L7 8TX, UK.
Andrew R BottrillProtein Nucleic Acid Laboratory, University of Leicester, Leicester, LE1 7RH, UK.
Adam A WitneyInstitute for Infection and Immunity, St George's University of London, London, SW17 0RE, UK.
Martin Cohen-GonsaudCentre de Biochimie Structurale, CNRS, INSERM, University of Montpellier, 34090, Montpellier, France.
Simon J WaddellWellcome Trust Brighton and Sussex Centre for Global Health Research, Brighton and Sussex Medical School, University of Sussex, Brighton, BN1 9PX, UK.
Galina V MukamolovaLeicester Tuberculosis Research Group, Department of Respiratory Sciences, University of Leicester, Leicester, LE2 9HN, UK.ORCID 0000-0001-5697-2018
University of Leicester · GBCentre National de la Recherche Scientifique · FRBrighton and Sussex Medical School · GBUniversity of Colorado Denver · USSt George's, University of London · GBUniversity of Liverpool · GB

Funding

Biotechnology and Biological Sciences Research Council BB/K000330/1Biotechnology and Biological Sciences Research Council BB/P001513/1Wellcome TrustWellcome Trust 204538/Z/16/Z
6 · The paper itself

Abstract

Mycobacterium tuberculosis (Mtb) is able to persist in the body through months of multi-drug therapy. Mycobacteria possess a wide range of regulatory proteins, including the protein kinase B (PknB) which controls peptidoglycan biosynthesis during growth. Here, we observed that depletion of PknB resulted in specific transcriptional changes that are likely caused by reduced phosphorylation of the H-NS-like regulator Lsr2 at threonine 112. The activity of PknB towards this phosphosite was confirmed with purified proteins, and this site was required for adaptation of Mtb to hypoxic conditions, and growth on solid media. Like H-NS, Lsr2 binds DNA in sequence-dependent and non-specific modes. PknB phosphorylation of Lsr2 reduced DNA binding, measured by fluorescence anisotropy and electrophoretic mobility shift assays, and our NMR structure of phosphomimetic T112D Lsr2 suggests that this may be due to increased dynamics of the DNA-binding domain. Conversely, the phosphoablative T112A Lsr2 had increased binding to certain DNA sites in ChIP-sequencing, and Mtb containing this variant showed transcriptional changes that correspond with the change in DNA binding. In summary, PknB controls Mtb growth and adaptations to the changing host environment by phosphorylating the global transcriptional regulator Lsr2.

Indexed as

Bacterial ProteinsChromatin Immunoprecipitation SequencingDNA-Binding ProteinsElectrophoretic Mobility Shift AssayGene Expression Regulation, BacterialMycobacterium tuberculosisPhosphorylationProto-Oncogene Proteins c-aktThreonineTranscription FactorsBacterial ProteinsDNA-Binding ProteinsLsr2 protein, Mycobacterium tuberculosisProto-Oncogene Proteins c-aktThreonineTranscription Factors

Identifiers

PMID31562654
PMCPMC6906086
OpenAlexW2976004976

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.