Evidence map›Paper›PMID 32474533›Full record

ArticleInternational journal of mycobacteriology

Determination of potentially novel compensatory mutations in rpoc associated with rifampin resistance and rpob mutations in

Ana Paula Vargas, Angela A Rios, Louis Grandjean, Daniela E Kirwan, Robert H Gilman, Patricia Sheen, Mirko J Zimic

Open access · diamondAbstract read
In one paragraph

Article in International journal of mycobacteriology. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
0.4field-weighted citation impact, top 25% 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

14 citing papers in PubMed, 27 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Dissecting rifampicin heteroresistance inJournal of medical microbiology · 2025
    Article
  5. Article
  6. Article
  7. Article
  8. Identification of positively selected genes inFrontiers in microbiology · 2024
    Article
  9. Article
  10. Acetylome and Succinylome Profiling ofAntibiotics (Basel, Switzerland) · 2022
    Article
  11. Article
  12. Review
  13. Article
  14. Low-Level Rifampin Resistance andJournal of clinical microbiology · 2021
    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

7 authors at 4 institutions in 3 countries.

Ana Paula VargasDepartment of Cellular and Molecular Sciences, Laboratory of Bioinformatics and Molecular Biology, Faculty of Science and Philosophy, Universidad Peruana Cayetano Heredia, Lima, Peru.
Angela A RiosDepartment of Cellular and Molecular Sciences, Laboratory of Bioinformatics and Molecular Biology, Faculty of Science and Philosophy, Universidad Peruana Cayetano Heredia, Lima, Peru.
Louis GrandjeanDepartment of Paediatric Infectious Diseases, Imperial College, University of London, London, England.
Daniela E KirwanInfection and Immunity Research Institute, St. George's, University of London, London, England.
Robert H GilmanDepartment of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
Patricia SheenDepartment of Cellular and Molecular Sciences, Laboratory of Bioinformatics and Molecular Biology, Faculty of Science and Philosophy, Universidad Peruana Cayetano Heredia, Lima, Peru.
Mirko J ZimicDepartment of Cellular and Molecular Sciences, Laboratory of Bioinformatics and Molecular Biology, Faculty of Science and Philosophy, Universidad Peruana Cayetano Heredia, Lima, Peru.
Universidad Peruana Cayetano Heredia · PEImperial College London · GBJohns Hopkins University · USSt George's, University of London · GB

Funding

Using the Mycobacterium tuberculosis Genome to Predict Tuberculosis Pathology, Drug Resistance Acquisition and Identify Community Transmission SitesR01AI146338 · NIAID · JOHNS HOPKINS UNIVERSITY · PI GILMAN, ROBERT H · 2020 to 2024
$3.3M
Medical Research Council MR/P019978/1Medical Research Council MR/P019978/2NIAID NIH HHS R01 AI146338Wellcome TrustWellcome Trust 099805/Z/12/Z
6 · The paper itself

Abstract

Background: Rifampicin (RIF) resistance in Mycobacterium tuberculosis is frequently caused by mutations in the rpoB gene. These mutations are associated with a fitness cost, which can be overcome by compensatory mutations in other genes, among which rpoC may be the most important. We analyzed 469 Peruvian M. tuberculosis clinical isolates to identify compensatory mutations in rpoC/rpoA associated with RIF resistance. Methods: The M. tuberculosis isolates were collected and tested for RIF susceptibility and spoligotyping. Samples were sequenced and aligned to the reference genome to identify mutations. By analyzing the sequences and the metadata, we identified a list of rpoC mutations exclusively associated with RIF resistance and mutations in rpoB. We then evaluated the distribution of these mutations along the protein sequence and tridimensional structure. Results: One hundred and twenty-five strains were RIF susceptible and 346 were resistant. We identified 35 potential new compensatory mutations, some of which were distributed on the interface surface between rpoB and rpoC, arising in clusters and suggesting the presence of hotspots for compensatory mutations. Conclusion: This study identifies 35 putative novel compensatory mutations in the β' subunit of M. tuberculosis RNApol. Six of these (S428T, L507V, A734V, I997V, and V1252LM) are considered most likely to have a compensatory role, as they fall in the interaction zone of the two subunits and the mutation did not lead to any change in the protein's physical-chemical properties.

Indexed as

Antitubercular AgentsBacterial ProteinsDNA-Directed RNA PolymerasesHumansMicrobial Sensitivity TestsMutationMycobacterium tuberculosisPeruRifampinTuberculosis, Multidrug-ResistantAntitubercular AgentsBacterial ProteinsDNA-Directed RNA PolymerasesRifampinrpoB protein, Mycobacterium tuberculosisCompensatory mutationsevolutionrifampicin resistancerpoBrpoCtuberculosi

Identifiers

PMID32474533
PMCPMC10022416
OpenAlexW3030043167

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.