Evidence map›Paper›PMID 31583725›Full record

ArticleThe EMBO journal2019

Preexisting variation in DNA damage response predicts the fate of single mycobacteria under stress.

Giulia Manina, Anna Griego, Lalit Kumar Singh, John D McKinney, Neeraj Dhar

Open access · bronzeAbstract read
In one paragraph

Article in The EMBO journal, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
1.8field-weighted citation impact, top 14% 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

24 citing papers in PubMed, 36 citations in OpenAlex.

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  14. Clinically encountered growth phenotypes of tuberculosis-causing bacilli and theirFrontiers in cellular and infection microbiology · 2022
    Review
  15. Listeriolysin S: A bacteriocin fromProceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  16. Article
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  19. Waddington's Landscapes in the Bacterial World.Frontiers in microbiology · 2021
    Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors at 3 institutions in 2 countries.

Giulia ManinaMicrobial Individuality and Infection Group, Cell Biology and Infection Department, Institut Pasteur, Paris, France.ORCID 0000-0001-9905-6095
Anna GriegoMicrobial Individuality and Infection Group, Cell Biology and Infection Department, Institut Pasteur, Paris, France.
Lalit Kumar SinghMicrobial Individuality and Infection Group, Cell Biology and Infection Department, Institut Pasteur, Paris, France.
John D McKinneySchool of Life Sciences, Swiss Federal Institute of Technology in Lausanne (EPFL), Lausanne, Switzerland.
Neeraj DharSchool of Life Sciences, Swiss Federal Institute of Technology in Lausanne (EPFL), Lausanne, Switzerland.ORCID 0000-0002-5887-8137
École Polytechnique Fédérale de Lausanne · CHInstitut Pasteur · FRDélégation Paris 5 · FR

Funding

Agence Nationale de la Recherche (ANR) ANR-10-LABX-62-IBEIDAgence Nationale de la Recherche (ANR) ANR-16-TERC-0011-01Agence Nationale de la Recherche (ANR) ANR-17-CE11-0007-01Fondation pour la Recherche Médicale ING20160435202Innovative Medicines Initiative (IMI) 115337
6 · The paper itself

Abstract

Clonal microbial populations are inherently heterogeneous, and this diversification is often considered as an adaptation strategy. In clinical infections, phenotypic diversity is found to be associated with drug tolerance, which in turn could evolve into genetic resistance. Mycobacterium tuberculosis, which ranks among the top ten causes of mortality with high incidence of drug-resistant infections, exhibits considerable phenotypic diversity. In this study, we quantitatively analyze the cellular dynamics of DNA damage responses in mycobacteria using microfluidics and live-cell fluorescence imaging. We show that individual cells growing under optimal conditions experience sporadic DNA-damaging events manifested by RecA expression pulses. Single-cell responses to these events occur as transient pulses of fluorescence expression, which are dependent on the gene-network structure but are triggered by extrinsic signals. We demonstrate that preexisting subpopulations, with discrete levels of DNA damage response, are associated with differential susceptibility to fluoroquinolones. Our findings reveal that the extent of DNA integrity prior to drug exposure impacts the drug activity against mycobacteria, with conceivable therapeutic implications.

Indexed as

Single-Cell AnalysisStress, PhysiologicalAnti-Bacterial AgentsBacterial ProteinsCiprofloxacinDNA DamageHumansMicrofluidicsMycobacterium tuberculosisRec A RecombinasesTuberculosisAnti-Bacterial AgentsBacterial ProteinsCiprofloxacinRec A RecombinasesDNA damagedrug persistencemicrofluidic microscopyphenotypic variationtuberculosis

Identifiers

PMID31583725
PMCPMC6856624
OpenAlexW2977665321

What OpenQuestion holds

Textmetadata
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.