Evidence map›Paper›PMID 35699226›Full record

ArticleNucleic acids research2022

Expression of Bacillus subtilis ABCF antibiotic resistance factor VmlR is regulated by RNA polymerase pausing, transcription attenuation, translation attenuation and (p)ppGpp.

Hiraku Takada, Zachary F Mandell, Helen Yakhnin, Anastasiya Glazyrina, Shinobu Chiba, Tatsuaki Kurata, Kelvin J Y Wu, Ben I C Tresco, Andrew G Myers, Gemma C Aktinson and 2 more

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
2.5field-weighted citation impact, top 8% 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

19 citing papers in PubMed, 40 citations in OpenAlex.

  1. Journal of microbiology and biotechnology · 2026
    Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Review
  8. Article
  9. Article
  10. Article
  11. The Resistance Abilities of SomeFood science & nutrition · 2025
    Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Allosteric mechanism of transcription inhibition by NusG-dependent pausing of RNA polymerase.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  18. Review
  19. 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

12 authors at 5 institutions in 4 countries.

Hiraku TakadaFaculty of Life Sciences, Kyoto Sangyo University and Institute for Protein Dynamics, Kamigamo, Motoyama, Kita-ku, Kyoto 603-8555, Japan.
Zachary F MandellDepartment of Biochemistry and Molecular Biology, Center for RNA Molecular Biology, Pennsylvania State University, University Park, PA, USA.
Helen YakhninDepartment of Biochemistry and Molecular Biology, Center for RNA Molecular Biology, Pennsylvania State University, University Park, PA, USA.
Anastasiya GlazyrinaDepartment of Molecular Biology, Umeå University, Building 6K, 6L University Hospital Area, 90187 Umeå, Sweden.
Shinobu ChibaFaculty of Life Sciences, Kyoto Sangyo University and Institute for Protein Dynamics, Kamigamo, Motoyama, Kita-ku, Kyoto 603-8555, Japan.ORCID 0000-0003-3485-3477
Tatsuaki KurataDepartment of Experimental Medical Science, Lund University, 221 00 Lund, Sweden.
Kelvin J Y WuDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.
Ben I C TrescoDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.
Andrew G MyersDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.
Gemma C AktinsonDepartment of Experimental Medical Science, Lund University, 221 00 Lund, Sweden.
Paul BabitzkeDepartment of Biochemistry and Molecular Biology, Center for RNA Molecular Biology, Pennsylvania State University, University Park, PA, USA.
Vasili HauryliukDepartment of Experimental Medical Science, Lund University, 221 00 Lund, Sweden.ORCID 0000-0003-2389-5057
Harvard University · USLund University · SEPennsylvania State University · USKyoto Sangyo University · JPUmeå University · SE

Funding

Regulation of transcription elongationR01GM098399 · NIGMS · PENNSYLVANIA STATE UNIVERSITY, THE · PI BABITZKE, PAUL L · 2012 to 2024
$3.6M
NIGMS NIH HHS R01 GM098399
6 · The paper itself

Abstract

Since antibiotic resistance is often associated with a fitness cost, bacteria employ multi-layered regulatory mechanisms to ensure that expression of resistance factors is restricted to times of antibiotic challenge. In Bacillus subtilis, the chromosomally-encoded ABCF ATPase VmlR confers resistance to pleuromutilin, lincosamide and type A streptogramin translation inhibitors. Here we show that vmlR expression is regulated by translation attenuation and transcription attenuation mechanisms. Antibiotic-induced ribosome stalling during translation of an upstream open reading frame in the vmlR leader region prevents formation of an anti-antiterminator structure, leading to the formation of an antiterminator structure that prevents intrinsic termination. Thus, transcription in the presence of antibiotic induces vmlR expression. We also show that NusG-dependent RNA polymerase pausing in the vmlR leader prevents leaky expression in the absence of antibiotic. Furthermore, we demonstrate that induction of VmlR expression by compromised protein synthesis does not require the ability of VmlR to rescue the translational defect, as exemplified by constitutive induction of VmlR by ribosome assembly defects. Rather, the specificity of induction is determined by the antibiotic's ability to stall the ribosome on the regulatory open reading frame located within the vmlR leader. Finally, we demonstrate the involvement of (p)ppGpp-mediated signalling in antibiotic-induced VmlR expression.

Indexed as

Anti-Bacterial AgentsBacillus subtilisBacterial ProteinsBase SequenceDNA-Directed RNA PolymerasesDrug Resistance, MicrobialGene Expression Regulation, BacterialGuanosine PentaphosphateR FactorsTranscription, GeneticAnti-Bacterial AgentsBacterial ProteinsDNA-Directed RNA PolymerasesGuanosine Pentaphosphate

Identifiers

PMID35699226
PMCPMC9226507
OpenAlexW4282835389

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.