Odilorhabdins, Antibacterial Agents that Cause Miscoding by Binding at a New Ribosomal Site
Copyright © 2018 Elsevier Inc. All rights reserved..
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.
| Errataetall: | |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2018 |
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| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:70 |
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| Enthalten in: |
Molecular cell - 70(2018), 1 vom: 05. Apr., Seite 83-94.e7 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Pantel, Lucile [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 14.01.2019 Date Revised 14.01.2019 published: Print CommentIn: Mol Cell. 2018 Apr 5;70(1):3-5. - PMID 29625037 Citation Status MEDLINE |
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| doi: |
10.1016/j.molcel.2018.03.001 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM282740937 |
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| 500 | |a CommentIn: Mol Cell. 2018 Apr 5;70(1):3-5. - PMID 29625037 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2018 Elsevier Inc. All rights reserved. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Racine, Emilie |e verfasserin |4 aut | |
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| 700 | 1 | |a Serri, Marine |e verfasserin |4 aut | |
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