Evidence map›Paper›PMID 26033726›Full record

ArticleAntimicrobial agents and chemotherapy2015

Molecular Analysis of the embCAB Locus and embR Gene Involved in Ethambutol Resistance in Clinical Isolates of Mycobacterium tuberculosis in France.

Florence Brossier, Wladimir Sougakoff, Christine Bernard, Matthieu Petrou, Karine Adeyema, Anne Pham, Diane Amy de la Breteque, Marine Vallet, Vincent Jarlier, Christophe Sola and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
3.7field-weighted citation impact, top 7% 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

36 citing papers in PubMed, 68 citations in OpenAlex.

  1. Article
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  4. Mutations inAntibiotics (Basel, Switzerland) · 2024
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  5. Genomic and phenotypic characterization ofMicrobiology spectrum · 2024
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  6. Identification ofInfection and drug resistance · 2024
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  8. Molecular Analysis of Anti-Tuberculosis Drug Resistance ofAntibiotics (Basel, Switzerland) · 2023
    Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Drug resistantPeerJ · 2022
    Article
  15. Article
  16. A Comprehensive Evaluation of GeneLEAD VIII DNA Platform Combined to Deeplex Myc-TBFrontiers in cellular and infection microbiology · 2021
    Article
  17. Frequency of Codon 306 Mutations inInternational journal of preventive medicine · 2020
    Review
  18. Detecting Ethambutol Resistance inFrontiers in microbiology · 2020
    Article
  19. Article
  20. Drug-resistance inMedChemComm · 2019
    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 7 institutions in 1 country.

Florence BrossierAP-HP, Hôpital Pitié-Salpêtrière, Centre National de Référence des Mycobactéries et de la Résistance des Mycobactéries aux Antituberculeux, Paris, France Sorbonne Universités, UPMC Université Paris 06, UMRS1135, Centre d'Immunologie et des Maladies Infectieuses, CIMI-Paris, Team 13 (Bacteriology), Paris, France INSERM, U1135, Centre d'Immunologie et des Maladies Infectieuses, CIMI-Paris, Team 13 (Bacteriology), Paris, France florence.brossier@psl.aphp.fr.
Wladimir SougakoffAP-HP, Hôpital Pitié-Salpêtrière, Centre National de Référence des Mycobactéries et de la Résistance des Mycobactéries aux Antituberculeux, Paris, France Sorbonne Universités, UPMC Université Paris 06, UMRS1135, Centre d'Immunologie et des Maladies Infectieuses, CIMI-Paris, Team 13 (Bacteriology), Paris, France INSERM, U1135, Centre d'Immunologie et des Maladies Infectieuses, CIMI-Paris, Team 13 (Bacteriology), Paris, France.
Christine BernardAP-HP, Hôpital Pitié-Salpêtrière, Centre National de Référence des Mycobactéries et de la Résistance des Mycobactéries aux Antituberculeux, Paris, France Sorbonne Universités, UPMC Université Paris 06, UMRS1135, Centre d'Immunologie et des Maladies Infectieuses, CIMI-Paris, Team 13 (Bacteriology), Paris, France INSERM, U1135, Centre d'Immunologie et des Maladies Infectieuses, CIMI-Paris, Team 13 (Bacteriology), Paris, France.
Matthieu PetrouInstitut de Génétique et Microbiologie, UMR8621 CNRS-Université Paris-Sud 11, UniverSud, Infection Genetics Emerging Pathogens Evolution (IGEPE) Team, Orsay, France.
Karine AdeyemaSorbonne Universités, UPMC Université Paris 06, UMRS1135, Centre d'Immunologie et des Maladies Infectieuses, CIMI-Paris, Team 13 (Bacteriology), Paris, France INSERM, U1135, Centre d'Immunologie et des Maladies Infectieuses, CIMI-Paris, Team 13 (Bacteriology), Paris, France.
Anne PhamSorbonne Universités, UPMC Université Paris 06, UMRS1135, Centre d'Immunologie et des Maladies Infectieuses, CIMI-Paris, Team 13 (Bacteriology), Paris, France INSERM, U1135, Centre d'Immunologie et des Maladies Infectieuses, CIMI-Paris, Team 13 (Bacteriology), Paris, France.
Diane Amy de la BretequeSorbonne Universités, UPMC Université Paris 06, UMRS1135, Centre d'Immunologie et des Maladies Infectieuses, CIMI-Paris, Team 13 (Bacteriology), Paris, France INSERM, U1135, Centre d'Immunologie et des Maladies Infectieuses, CIMI-Paris, Team 13 (Bacteriology), Paris, France.
Marine ValletSorbonne Universités, UPMC Université Paris 06, UMRS1135, Centre d'Immunologie et des Maladies Infectieuses, CIMI-Paris, Team 13 (Bacteriology), Paris, France INSERM, U1135, Centre d'Immunologie et des Maladies Infectieuses, CIMI-Paris, Team 13 (Bacteriology), Paris, France.
Vincent JarlierAP-HP, Hôpital Pitié-Salpêtrière, Centre National de Référence des Mycobactéries et de la Résistance des Mycobactéries aux Antituberculeux, Paris, France Sorbonne Universités, UPMC Université Paris 06, UMRS1135, Centre d'Immunologie et des Maladies Infectieuses, CIMI-Paris, Team 13 (Bacteriology), Paris, France INSERM, U1135, Centre d'Immunologie et des Maladies Infectieuses, CIMI-Paris, Team 13 (Bacteriology), Paris, France.
Christophe SolaInstitut de Génétique et Microbiologie, UMR8621 CNRS-Université Paris-Sud 11, UniverSud, Infection Genetics Emerging Pathogens Evolution (IGEPE) Team, Orsay, France.
Nicolas VezirisAP-HP, Hôpital Pitié-Salpêtrière, Centre National de Référence des Mycobactéries et de la Résistance des Mycobactéries aux Antituberculeux, Paris, France Sorbonne Universités, UPMC Université Paris 06, UMRS1135, Centre d'Immunologie et des Maladies Infectieuses, CIMI-Paris, Team 13 (Bacteriology), Paris, France INSERM, U1135, Centre d'Immunologie et des Maladies Infectieuses, CIMI-Paris, Team 13 (Bacteriology), Paris, France.
Sorbonne Université · FRCentre d'Immunologie et des Maladies Infectieuses · FRInserm · FRAssistance Publique – Hôpitaux de Paris · FRCentre National de la Recherche Scientifique · FRCNR de la Résistance aux Antibiotiques · FRUniversité Paris-Sud · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Modification of codon 306 in embB is regarded as the main mechanism leading to ethambutol (ETB) resistance in clinical isolates of Mycobacterium tuberculosis. However, numerous mutations elsewhere in the embCAB locus and in embR, a putative transcriptional activator of this locus, have been reported to be involved in ETB resistance. Here, we investigated the diversity of nucleotide variations observed in embCAB and embR in M. tuberculosis complex isolates from France. These regions were sequenced in 71 ETB-resistant (ETB-R) and 60 ETB-susceptible (ETB-S) clinical isolates of known phylogenetic lineages. The 131 isolates had 12 mutations corresponding to phylogenetic markers. Among the 60 ETB-S isolates, only 3 (5%) had nonsynonymous mutations that were not phylogenetic markers. Among the 71 ETB-R isolates, 98% had mutations in embCAB that likely contribute to ETB resistance: 70% had mutations located in embB codon 306, 406, or 497; 13% had mutations located outside these three positions between codons 296 and 426; and 15% had mutations corresponding to mutations in the embC-embA intergenic region. We found a strong association between resistance to ETB and the presence of mutations in embB and the embC-embA intergenic region (P < 0.001). In contrast, the mutations detected in embC and embA were not involved in ETB resistance, and no mutation was detected in embR. These results strongly suggest that the sensitivity of diagnostic assays for detecting ETB resistance based on testing of embB codon 306 can be increased by testing of the embB region between codons 296 and 497 and by including the embC-embA intergenic region between positions -8 and -21.

Indexed as

Antitubercular AgentsCodonDNA, BacterialDNA, IntergenicDrug Resistance, BacterialEthambutolGenes, BacterialGenetic VariationHumansMicrobial Sensitivity TestsMutationMycobacterium tuberculosisPhylogenyTrans-ActivatorsAntitubercular AgentsCodonDNA, BacterialDNA, IntergenicEthambutolTrans-Activators

Identifiers

PMID26033726
PMCPMC4505224
OpenAlexW1917166617

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