Evidence map›Paper›PMID 34633851›Full record

ArticleAntimicrobial agents and chemotherapy2022

RNA Sequencing Elucidates Drug-Specific Mechanisms of Antibiotic Tolerance and Resistance in Mycobacterium abscessus.

Jodie A Schildkraut, Jordy P M Coolen, Sophie Burbaud, Jasper J N Sangen, Michael P Kwint, R Andres Floto, Huub J M Op den Camp, Lindsey H M Te Brake, Heiman F L Wertheim, Kornelia Neveling and 2 more

Open access · hybridAbstract read
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed, 1 pooled it
2.3field-weighted citation impact, top 11% 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

18 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.

  1. A systematic review of tetracyclines for nontuberculous mycobacteria: focus on rapidly growing mycobacteria.European respiratory review : an official journal of the European Respiratory Society · 2025
    Pooled it
  2. Review
  3. Molecular Mechanisms Underlying Antimicrobial Resistance in Mycobacteria.International journal of molecular sciences · 2026
    Review
  4. Article
  5. Article
  6. Article
  7. Mechanistic Studies of Antibacterial PNAs by RNA-Seq Analysis.Methods in molecular biology (Clifton, N.J.) · 2026
    Article
  8. Article
  9. Article
  10. A viable but nonculturable state ofJournal of medical microbiology · 2025
    Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Unusually high clarithromycin resistance inFrontiers in microbiology · 2023
    Article
  16. Transcriptome Analysis ofInternational journal of environmental research and public health · 2022
    Article
  17. Genetic Determinants of Tigecycline Resistance inAntibiotics (Basel, Switzerland) · 2022
    Review
  18. Recent Advances in Structural Studies of CytochromeInternational journal of molecular sciences · 2022
    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

12 authors at 2 institutions in 2 countries.

Jodie A SchildkrautRadboudumc Center for Infectious Diseases, Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, the Netherlands.ORCID 0000-0002-7236-8934
Jordy P M CoolenRadboudumc Center for Infectious Diseases, Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, the Netherlands.ORCID 0000-0003-0443-6250
Sophie BurbaudUniversity of Cambridge Molecular Immunity Unit, Department of Medicine, Cambridge, United Kingdom.
Jasper J N SangenUniversity of Cambridge Molecular Immunity Unit, Department of Medicine, Cambridge, United Kingdom.
Michael P KwintDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
R Andres FlotoUniversity of Cambridge Molecular Immunity Unit, Department of Medicine, Cambridge, United Kingdom.
Huub J M Op den CampDepartment of Microbiology, IWWR, Radboud University, Nijmegen, the Netherlands.ORCID 0000-0003-1990-9030
Lindsey H M Te BrakeRadboudumc Center for Infectious Diseases, Department of Pharmacy, Radboud University Medical Center, Nijmegen, the Netherlands.
Heiman F L WertheimRadboudumc Center for Infectious Diseases, Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, the Netherlands.
Kornelia NevelingDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
Wouter HoefslootRadboudumc Center for Infectious Diseases, Department of Pulmonary diseases, Radboud University Medical Center, Nijmegen, the Netherlands.
Jakko van IngenRadboudumc Center for Infectious Diseases, Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, the Netherlands.ORCID 0000-0002-0581-2003
Radboud University Nijmegen · NLUniversity of Cambridge · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Mycobacterium abscessus is an opportunistic pathogen notorious for its resistance to most classes of antibiotics and low cure rates. M. abscessus carries an array of mostly unexplored defense mechanisms. A deeper understanding of antibiotic resistance and tolerance mechanisms is pivotal in development of targeted therapeutic regimens. We provide the first description of all major transcriptional mechanisms of tolerance to all antibiotics recommended in current guidelines, using RNA sequencing-guided experiments. M. abscessus ATCC 19977 bacteria were subjected to subinhibitory concentrations of clarithromycin (CLR), amikacin (AMK), tigecycline (TIG), cefoxitin (FOX), and clofazimine (CFZ) for 4 and 24 h, followed by RNA sequencing. To confirm key mechanisms of tolerance suggested by transcriptomic responses, we performed time-kill kinetic analysis using bacteria after preexposure to CLR, AMK, or TIG for 24 h and constructed isogenic knockout and knockdown strains. To assess strain specificity, pan-genome analysis of 35 strains from all three subspecies was performed. Mycobacterium abscessus shows both drug-specific and common transcriptomic responses to antibiotic exposure. Ribosome-targeting antibiotics CLR, AMK, and TIG elicit a common response characterized by upregulation of ribosome structural genes, the

Indexed as

Mycobacterium abscessusMycobacterium Infections, NontuberculousAnti-Bacterial AgentsClarithromycinHumansKineticsMicrobial Sensitivity TestsRNASequence Analysis, RNAAnti-Bacterial AgentsClarithromycinRNAantibiotic resistanceM. abscessusnontuberculous mycobacteriaRNA sequencing

Identifiers

PMID34633851
PMCPMC8765290
OpenAlexW3207291566

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.