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TitleGenome-encoded ABCF factors implicated in intrinsic antibiotic resistance in Gram-positive bacteria: VmlR2, Ard1 and CplR.
Journal, issue, pagesNucleic Acids Res, Vol. 51, Issue 9, Page 4536-4554, Year 2023
Publish dateMar 23, 2023
AuthorsNozomu 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 / Nobuhiko Nomura / Andrew G Myers / Gemma C Atkinson / Daniel N Wilson / Vasili Hauryliuk /
PubMed AbstractGenome-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 ...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.
External linksNucleic Acids Res / PubMed:36951104 / PubMed Central
MethodsEM (single particle)
Resolution2.9 Å
Structure data

16246

8buu

EMDB-16246, PDB-8buu:
ARE-ABCF VmlR2 bound to a 70S ribosome
Method: EM (single particle) / Resolution: 2.9 Å

Chemicals

ChemComp-K:
Unknown entry

ChemComp-MG:
Unknown entry

ChemComp-ZN:
Unknown entry

ChemComp-ATP:
ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying molecule*YM / Adenosine triphosphate

Source
  • neobacillus vireti (bacteria)
  • bacillus subtilis subsp. subtilis str. 168 (bacteria)
KeywordsRIBOSOME / ABC / ABCF / ABC-F / VmlR2 / antibiotic resistance / initiation / distorted P-tRNA / Shina-Dalgarno / Neobacillus vireti / Bacillus subtilis

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