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  • Pantel, LucileNosopharm, Espace Innovat 2, 110 Allee Charles Babbage, F-30000 Nimes, France (author)

Odilorhabdins, Antibacterial Agents that Cause Miscoding by Binding at a New Ribosomal Site

  • Article/chapterEnglish2018

Publisher, publication year, extent ...

  • CELL PRESS,2018
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-352693
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-352693URI
  • https://doi.org/10.1016/j.molcel.2018.03.001DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Growing resistance of pathogenic bacteria and shortage of antibiotic discovery platforms challenge the use of antibiotics in the clinic. This threat calls for exploration of unconventional sources of antibiotics and identification of inhibitors able to eradicate resistant bacteria. Here we describe a different class of antibiotics, odilorhabdins (ODLs), produced by the enzymes of the non-ribosomal peptide synthetase gene cluster of the nematode-symbiotic bacterium Xenorhabdus nematophila. ODLs show activity against Gram-positive and Gram-negative pathogens, including carbapenem-resistant Enterobacteriaceae, and can eradicate infections in animal models. We demonstrate that the bactericidal ODLs interfere with protein synthesis. Genetic and structural analyses reveal that ODLs bind to the small ribosomal subunit at a site not exploited by current antibiotics. ODLs induce miscoding and promote hungry codon readthrough, amino acid misincorporation, and premature stop codon bypass. We propose that ODLs' miscoding activity reflects their ability to increase the affinity of non-cognate aminoacyl-tRNAs to the ribosome.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Florin, TanjaUniv Illinois, Ctr Biomol Sci, Chicago, IL 60607 USA (author)
  • Dobosz-Bartoszek, MalgorzataUniv Illinois, Dept Biol Sci, Chicago, IL 60607 USA (author)
  • Racine, EmilieNosopharm, Espace Innovat 2, 110 Allee Charles Babbage, F-30000 Nimes, France (author)
  • Sarciaux, MatthieuNosopharm, Espace Innovat 2, 110 Allee Charles Babbage, F-30000 Nimes, France (author)
  • Serri, MarineNosopharm, Espace Innovat 2, 110 Allee Charles Babbage, F-30000 Nimes, France (author)
  • Houard, JessicaNosopharm, Espace Innovat 2, 110 Allee Charles Babbage, F-30000 Nimes, France (author)
  • Campagne, Jean-MarcCNRS, ENSCM, Inst Charles Gerhardt Montpellier, UMR 5253,UM, Montpellier, France (author)
  • de Figueiredo, Renata MarciaCNRS, ENSCM, Inst Charles Gerhardt Montpellier, UMR 5253,UM, Montpellier, France (author)
  • Midrier, CamilleCNRS, ENSCM, Inst Charles Gerhardt Montpellier, UMR 5253,UM, Montpellier, France (author)
  • Gaudriault, SophieUniv Montpellier, INRA, DGIMI, Montpellier, France (author)
  • Givaudan, AlainUniv Montpellier, INRA, DGIMI, Montpellier, France (author)
  • Lanois, AnneUniv Montpellier, INRA, DGIMI, Montpellier, France (author)
  • Forst, SteveUniv Wisconsin, Dept Biol Sci, POB 413, Milwaukee, WI 53201 USA (author)
  • Aumelas, AndreNosopharm, Espace Innovat 2, 110 Allee Charles Babbage, F-30000 Nimes, France (author)
  • Cotteaux-Lautard, ChristelleAix Marseille Univ, IRBA, Fac Med, TMCD2,UMR MD1, Marseille, France (author)
  • Bolla, Jean-MichelAix Marseille Univ, IRBA, Fac Med, TMCD2,UMR MD1, Marseille, France (author)
  • Lundberg, Carina VingsboStatens Serum Inst, Bacteria Parasites & Fungi, DK-2300 Copenhagen, Denmark (author)
  • Huseby, Douglas LUppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi(Swepub:uu)douhu661 (author)
  • Hughes, Diarmaid,1956-Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi(Swepub:uu)diarhugh (author)
  • Villain-Guillot, PhilippeNosopharm, Espace Innovat 2, 110 Allee Charles Babbage, F-30000 Nimes, France (author)
  • Mankin, Alexander S.Univ Illinois, Ctr Biomol Sci, Chicago, IL 60607 USA (author)
  • Polikanov, Yury S.Univ Illinois, Dept Biol Sci, Chicago, IL 60607 USA;Univ Illinois, Dept Med Chem & Pharmacognosy, Chicago, IL 60607 USA (author)
  • Gualtieri, MaximeNosopharm, Espace Innovat 2, 110 Allee Charles Babbage, F-30000 Nimes, France (author)
  • Nosopharm, Espace Innovat 2, 110 Allee Charles Babbage, F-30000 Nimes, FranceUniv Illinois, Ctr Biomol Sci, Chicago, IL 60607 USA (creator_code:org_t)

Related titles

  • In:Molecular Cell: CELL PRESS70:1, s. 83-941097-27651097-4164

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