Evidence map›Paper›PMID 28704501›Full record

ArticlePloS one2017

Reduced susceptibility of clinical strains of Mycobacterium tuberculosis to reactive nitrogen species promotes survival in activated macrophages.

Jonna Idh, Blanka Andersson, Maria Lerm, Johanna Raffetseder, Daniel Eklund, Hanna Woksepp, Jim Werngren, Mikael Mansjö, Tommy Sundqvist, Olle Stendahl and 1 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.0field-weighted citation impact, top 26% 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

6 citing papers in PubMed, 17 citations in OpenAlex.

  1. Review
  2. Review
  3. Offense and Defense in Granulomatous Inflammation Disease.Frontiers in cellular and infection microbiology · 2022
    Review
  4. Article
  5. Review
  6. Review
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

11 authors at 3 institutions in 1 country.

Jonna IdhDivision of Microbiology and Molecular Medicine, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Blanka AnderssonDivision of Microbiology and Molecular Medicine, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Maria LermDivision of Microbiology and Molecular Medicine, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Johanna RaffetsederDivision of Microbiology and Molecular Medicine, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Daniel EklundDivision of Microbiology and Molecular Medicine, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Hanna WokseppDepartment of Optometry and Medicine, Linneaus University, Kalmar, Sweden.
Jim WerngrenDepartment of Microbiology, Unit for Laboratory Surveillance of Bacterial Pathogens, Public Health Agency of Sweden, Solna, Sweden.
Mikael MansjöDepartment of Microbiology, Unit for Laboratory Surveillance of Bacterial Pathogens, Public Health Agency of Sweden, Solna, Sweden.
Tommy SundqvistDivision of Microbiology and Molecular Medicine, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Olle StendahlDivision of Microbiology and Molecular Medicine, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Thomas SchönDivision of Microbiology and Molecular Medicine, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.ORCID http://orcid.org/0000-0003-4849-1286
Linköping University · SEPublic Health Agency of Sweden · SELinnaeus University · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundDrugs such as isoniazid (INH) and pretomanid (PRT), used against Mycobacterium tuberculosis are active partly through generation of reactive nitrogen species (RNS). The aim of this study was to explore variability in intracellular susceptibility to nitric oxide (NO) in clinical strains of M. tuberculosis.

methodLuciferase-expressing clinical M. tuberculosis strains with or without INH resistance were exposed to RNS donors (DETA/NO and SIN-1) in broth cultures and bacterial survival was analysed by luminometry. NO-dependent intracellular killing in a selection of strains was assessed in interferon gamma/lipopolysaccharide-activated murine macrophages using the NO inhibitor L-NMMA.

resultsWhen M. tuberculosis H37Rv was compared to six clinical isolates and CDC1551, three isolates with inhA mediated INH resistance showed significantly reduced NO-susceptibility in broth culture. All strains showed a variable but dose-dependent susceptibility to RNS donors. Two clinical isolates with increased susceptibility to NO exposure in broth compared to H37Rv were significantly inhibited by activated macrophages whereas there was no effect on growth inhibition when activated macrophages were infected by clinical strains with higher survival to NO exposure in broth. Furthermore, the most NO-tolerant clinical isolate showed increased resistance to PRT both in broth culture and the macrophage model compared to H37Rv in the absence of mutational resistance in genes associated to reduced susceptibility against PRT or NO.

conclusionIn a limited number of clinical M. tuberculosis isolates we found a significant difference in susceptibility to NO between clinical isolates, both in broth cultures and in macrophages. Our results indicate that mycobacterial susceptibility to cellular host defence mechanisms such as NO need to be taken into consideration when designing new therapeutic strategies.

Indexed as

AnimalsAntitubercular AgentsCells, CulturedDrug Resistance, BacterialMacrophage ActivationMacrophagesMiceMicrobial Sensitivity TestsMicrobial ViabilityMycobacterium tuberculosisNitric OxideOrganisms, Genetically ModifiedPeroxynitrous AcidReactive Nitrogen SpeciesAntitubercular AgentsNitric OxidePeroxynitrous AcidReactive Nitrogen Species

Identifiers

PMID28704501
PMCPMC5509328
OpenAlexW2734828914

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.