Genome-encoded ABCF factors implicated in intrinsic antibiotic resistance in Gram-positive bacteria: VmlR2, Ard1 and CplR
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- Nozomu Obana
- Transborder Medical Research Center, Faculty of Medicine, University of Tsukuba , Tsukuba , Japan
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- Hiraku Takada
- Faculty of Life Sciences, Kyoto Sangyo University , Motoyama, Kamigamo, Kita-Ku, Kyoto 603-8555, Japan
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- Caillan Crowe-McAuliffe
- Institute for Biochemistry and Molecular Biology, University of Hamburg , Martin-Luther-King-Platz 6, 20146 Hamburg , Germany
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- Mizuki Iwamoto
- Faculty of Life and Environmental Sciences, University of Tsukuba , Tsukuba , Japan
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- Artyom A Egorov
- Department of Experimental Medical Science, Lund University , Lund , Sweden
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- Kelvin J Y Wu
- Department of Chemistry and Chemical Biology, Harvard University , Cambridge , MA , USA
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- Shinobu Chiba
- Faculty of Life Sciences, Kyoto Sangyo University , Motoyama, Kamigamo, Kita-Ku, Kyoto 603-8555, Japan
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- Victoriia Murina
- Department of Molecular Biology, Umeå University , Umeå , Sweden
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- Helge Paternoga
- Institute for Biochemistry and Molecular Biology, University of Hamburg , Martin-Luther-King-Platz 6, 20146 Hamburg , Germany
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- Ben I C Tresco
- Department of Chemistry and Chemical Biology, Harvard University , Cambridge , MA , USA
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- Nobuhiko Nomura
- Microbiology Research Center for Sustainability (MiCS), University of Tsukuba , Tsukuba , Japan
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- Andrew G Myers
- Department of Chemistry and Chemical Biology, Harvard University , Cambridge , MA , USA
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- Gemma C Atkinson
- Department of Experimental Medical Science, Lund University , Lund , Sweden
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- Daniel N Wilson
- Institute for Biochemistry and Molecular Biology, University of Hamburg , Martin-Luther-King-Platz 6, 20146 Hamburg , Germany
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- Vasili Hauryliuk
- Department of Experimental Medical Science, Lund University , Lund , Sweden
抄録
<jats:title>Abstract</jats:title> <jats:p>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.</jats:p>
収録刊行物
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- Nucleic Acids Research
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Nucleic Acids Research 51 (9), 4536-4554, 2023-03-23
Oxford University Press (OUP)
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詳細情報 詳細情報について
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- CRID
- 1360579819981601792
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- ISSN
- 13624962
- 03051048
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- データソース種別
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- Crossref
- KAKEN