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

Author:

Obana Nozomu12,Takada Hiraku34,Crowe-McAuliffe Caillan5,Iwamoto Mizuki6,Egorov Artyom A4,Wu Kelvin J Y7,Chiba Shinobu38ORCID,Murina Victoriia9,Paternoga Helge5,Tresco Ben I C7,Nomura Nobuhiko26,Myers Andrew G7,Atkinson Gemma C4,Wilson Daniel N5ORCID,Hauryliuk Vasili41011ORCID

Affiliation:

1. Transborder Medical Research Center, Faculty of Medicine, University of Tsukuba , Tsukuba , Japan

2. Microbiology Research Center for Sustainability (MiCS), University of Tsukuba , Tsukuba , Japan

3. Faculty of Life Sciences, Kyoto Sangyo University , Motoyama, Kamigamo, Kita-Ku, Kyoto  603-8555, Japan

4. Department of Experimental Medical Science, Lund University , Lund , Sweden

5. Institute for Biochemistry and Molecular Biology, University of Hamburg , Martin-Luther-King-Platz 6, 20146  Hamburg , Germany

6. Faculty of Life and Environmental Sciences, University of Tsukuba , Tsukuba , Japan

7. Department of Chemistry and Chemical Biology, Harvard University , Cambridge , MA , USA

8. Institute for Protein Dynamics, Kyoto Sangyo University , Japan

9. Department of Molecular Biology, Umeå University , Umeå , Sweden

10. University of Tartu, Institute of Technology , Tartu , Estonia

11. Science for Life Laboratory , Lund , Sweden

Abstract

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.

Funder

DFG

Swedish Research Council

Estonian Research Council

National Institutes of Health

Centre of Excellence in Molecular Cell Engineering

Deutsche Zentrum für Luft- und Raumfahrt

Knut and Alice Wallenberg Foundation

Scientific Research

Institute for Fermentation, Osaka

Publisher

Oxford University Press (OUP)

Subject

Genetics

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3