Evidence map›Paper›PMID 26295942›Full record

ArticlePloS one2015

Confinement-Induced Drug-Tolerance in Mycobacteria Mediated by an Efflux Mechanism.

Brilliant B Luthuli, Georgiana E Purdy, Frederick K Balagaddé

Abstract read
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

4 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Phenotypic adaptation ofFrontiers in cellular and infection microbiology · 2022
    Review
  3. Review
  4. 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

3 authors.

Brilliant B LuthuliKwaZulu-Natal Research Institute for Tuberculosis and HIV, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, 4001, South Africa.
Georgiana E PurdyDept. of Molecular Microbiology and Immunology, Oregon Health and Sciences University, 3181 S. W. Sam Jackson Park Rd., Mail Code L220, Portland, OR, 97239, United States of America.
Frederick K BalagaddéKwaZulu-Natal Research Institute for Tuberculosis and HIV, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, 4001, South Africa.

Funding

TB Membrane Transporters and Intrinsic ResistanceR01AI087840 · NIAID · OREGON HEALTH & SCIENCE UNIVERSITY · PI PURDY, GEORGIANA E. · 2011 to 2015
$1.9M
Howard Hughes Medical InstituteNIAID NIH HHS R01 AI087840
6 · The paper itself

Abstract

Tuberculosis (TB) is the world's deadliest curable disease, responsible for an estimated 1.5 million deaths annually. A considerable challenge in controlling this disease is the prolonged multidrug chemotherapy (6 to 9 months) required to overcome drug-tolerant mycobacteria that persist in human tissues, although the same drugs can sterilize genetically identical mycobacteria growing in axenic culture within days. An essential component of TB infection involves intracellular Mycobacterium tuberculosis bacteria that multiply within macrophages and are significantly more tolerant to antibiotics compared to extracellular mycobacteria. To investigate this aspect of human TB, we created a physical cell culture system that mimics confinement of replicating mycobacteria, such as in a macrophage during infection. Using this system, we uncovered an epigenetic drug-tolerance phenotype that appears when mycobacteria are cultured in space-confined bioreactors and disappears in larger volume growth contexts. Efflux mechanisms that are induced in space-confined growth environments contribute to this drug-tolerance phenotype. Therefore, macrophage-induced drug tolerance by mycobacteria may be an effect of confined growth among other macrophage-specific mechanisms.

Indexed as

Lab-On-A-Chip DevicesModels, BiologicalAntitubercular AgentsBacterial LoadBiological TransportCinnamatesDiffusionDimethylpolysiloxanesDrug ToleranceEpigenesis, GeneticHumansHygromycin BIsoniazidMacrophagesMicrodialysisMycobacterium smegmatisAntitubercular AgentsbaysilonCinnamatesDimethylpolysiloxaneshygromycin AHygromycin BIsoniazidOfloxacinRifampin

Identifiers

PMID26295942
PMCPMC4546595

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.