Evidence map›Paper›PMID 36951104›Full record

ArticleNucleic acids research2023

Genome-encoded ABCF factors implicated in intrinsic antibiotic resistance in Gram-positive bacteria: VmlR2, Ard1 and CplR.

Nozomu Obana, Hiraku Takada, Caillan Crowe-McAuliffe, Mizuki Iwamoto, Artyom A Egorov, Kelvin J Y Wu, Shinobu Chiba, Victoriia Murina, Helge Paternoga, Ben I C Tresco and 5 more

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
3.3field-weighted citation impact, top 6% 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

21 citing papers in PubMed, 36 citations in OpenAlex.

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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

15 authors at 6 institutions in 5 countries.

Nozomu ObanaTransborder Medical Research Center, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
Hiraku TakadaFaculty of Life Sciences, Kyoto Sangyo University, Motoyama, Kamigamo, Kita-Ku, Kyoto 603-8555, Japan.
Caillan Crowe-McAuliffeInstitute for Biochemistry and Molecular Biology, University of Hamburg, Martin-Luther-King-Platz 6, 20146 Hamburg, Germany.
Mizuki IwamotoFaculty of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Japan.
Artyom A EgorovDepartment of Experimental Medical Science, Lund University, Lund, Sweden.
Kelvin J Y WuDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.
Shinobu ChibaFaculty of Life Sciences, Kyoto Sangyo University, Motoyama, Kamigamo, Kita-Ku, Kyoto 603-8555, Japan.ORCID 0000-0003-3485-3477
Victoriia MurinaDepartment of Molecular Biology, Umeå University, Umeå, Sweden.
Helge PaternogaInstitute for Biochemistry and Molecular Biology, University of Hamburg, Martin-Luther-King-Platz 6, 20146 Hamburg, Germany.
Ben I C TrescoDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.
Nobuhiko NomuraMicrobiology Research Center for Sustainability (MiCS), University of Tsukuba, Tsukuba, Japan.
Andrew G MyersDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.
Gemma C AtkinsonDepartment of Experimental Medical Science, Lund University, Lund, Sweden.
Daniel N WilsonInstitute for Biochemistry and Molecular Biology, University of Hamburg, Martin-Luther-King-Platz 6, 20146 Hamburg, Germany.ORCID 0000-0003-3816-3828
Vasili HauryliukDepartment of Experimental Medical Science, Lund University, Lund, Sweden.ORCID 0000-0003-2389-5057
Harvard University · USLund University · SEUniversität Hamburg · DEUniversity of Tsukuba · JPKyoto Sangyo University · JPUmeå University · SE

Funding

Discovery through chemical synthesis of antibiotics effective against modern bacterial pathogensR01AI168228 · NIAID · HARVARD UNIVERSITY · PI ANDREW G MYERS · 2022 to 2026
$3.8M
NIAID NIH HHS R01 AI168228NIH HHS R01AI168228
6 · The paper itself

Abstract

Genome-encoded antibiotic resistance (ARE) ATP-binding cassette (ABC) proteins of the F subfamily (ARE-ABCFs) mediate intrinsic resistance in diverse Gram-positive bacteria. The diversity of chromosomally-encoded ARE-ABCFs is far from being fully experimentally explored. Here we characterise phylogenetically diverse genome-encoded ABCFs from Actinomycetia (Ard1 from Streptomyces capreolus, producer of the nucleoside antibiotic A201A), Bacilli (VmlR2 from soil bacterium Neobacillus vireti) and Clostridia (CplR from Clostridium perfringens, Clostridium sporogenes and Clostridioides difficile). We demonstrate that Ard1 is a narrow spectrum ARE-ABCF that specifically mediates self-resistance against nucleoside antibiotics. The single-particle cryo-EM structure of a VmlR2-ribosome complex allows us to rationalise the resistance spectrum of this ARE-ABCF that is equipped with an unusually long antibiotic resistance determinant (ARD) subdomain. We show that CplR contributes to intrinsic pleuromutilin, lincosamide and streptogramin A resistance in Clostridioides, and demonstrate that C. difficile CplR (CDIF630_02847) synergises with the transposon-encoded 23S ribosomal RNA methyltransferase Erm to grant high levels of antibiotic resistance to the C. difficile 630 clinical isolate. Finally, assisted by uORF4u, our novel tool for detection of upstream open reading frames, we dissect the translational attenuation mechanism that controls the induction of cplR expression upon an antibiotic challenge.

Indexed as

Anti-Bacterial AgentsDrug Resistance, BacterialGenes, BacterialGram-Positive BacteriaActinobacteriaBacterial ProteinsClostridioides difficileClostridiumCryoelectron MicroscopyMethyltransferasesNucleosidesAnti-Bacterial AgentsBacterial ProteinsErmA protein, BacteriaMethyltransferasesNucleosides

Identifiers

PMID36951104
PMCPMC10201436
OpenAlexW4353112026

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.