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Micrococcin P1-A ba...
Micrococcin P1-A bactericidal thiopeptide active against Mycobacterium tuberculosis
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- Degiacomi, Giulia (author)
- Univ Padua, Dept Mol Med, Via Gabelli 63, I-35121 Padua, Italy.
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- Personne, Yoann (author)
- Queen Mary Univ London, London E1 2AD, England.;UCL, Div Infect & Immun, Ctr Clin Microbiol, London, England.
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- Mondesert, Guillaume (author)
- Sanofi Aventis R&D, Drug Disposit, F-69367 Lyon, France.
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- Ge, Xueliang (author)
- Uppsala universitet,Struktur- och molekylärbiologi
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- Mandava, Chandra Sekhar, 1978- (author)
- Uppsala universitet,Struktur- och molekylärbiologi
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- Hartkoorn, Ruben C. (author)
- Ecole Polytech Fed Lausanne, Global Hlth Inst, Lausanne, Switzerland.;Univ Lille Nord France, Inst Pasteur Lille, Ctr Infect & Immun Lille, INSERM,CNRS,UMR 8204,U1019, Lille, France.
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- Boldrin, Francesca (author)
- Univ Padua, Dept Mol Med, Via Gabelli 63, I-35121 Padua, Italy.
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- Goel, Pavitra (author)
- Queen Mary Univ London, London E1 2AD, England.
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- Peisker, Kristin (author)
- Uppsala universitet,Institutionen för cell- och molekylärbiologi
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- Benjak, Andrej (author)
- Ecole Polytech Fed Lausanne, Global Hlth Inst, Lausanne, Switzerland.
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- Barrio, Maria Belen (author)
- Sanofi Aventis R&D, Drug Disposit, F-69367 Lyon, France.
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- Ventura, Marcello (author)
- Univ Padua, Dept Mol Med, Via Gabelli 63, I-35121 Padua, Italy.
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- Brown, Amanda C. (author)
- Queen Mary Univ London, London E1 2AD, England.;Cornell Univ, Dept Microbiol & Immunol, Ithaca, NY 14853 USA.
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- Leblanc, Veronique (author)
- Sanofi Aventis R&D, Drug Disposit, F-69367 Lyon, France.
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- Bauer, Armin (author)
- Sanofi Aventis R&D, Drug Disposit, F-69367 Lyon, France.
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- Sanyal, Suparna (author)
- Uppsala universitet,Institutionen för cell- och molekylärbiologi
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- Cole, Stewart T. (author)
- Ecole Polytech Fed Lausanne, Global Hlth Inst, Lausanne, Switzerland.
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- Lagrange, Sophie (author)
- Sanofi Aventis R&D, Drug Disposit, F-69367 Lyon, France.
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- Parish, Tanya (author)
- Queen Mary Univ London, London E1 2AD, England.;Infect Dis Res Inst, TB Discovery Res, Seattle, WA 98102 USA.
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- Manganelli, Riccardo (author)
- Univ Padua, Dept Mol Med, Via Gabelli 63, I-35121 Padua, Italy.
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Univ Padua, Dept Mol Med, Via Gabelli 63, I-35121 Padua, Italy Queen Mary Univ London, London E1 2AD, England.;UCL, Div Infect & Immun, Ctr Clin Microbiol, London, England. (creator_code:org_t)
- Elsevier BV, 2016
- 2016
- English.
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In: Tuberculosis. - : Elsevier BV. - 1472-9792 .- 1873-281X. ; 100, s. 95-101
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- The lack of proper treatment for serious infectious diseases due to the emergence of multidrug resistance reinforces the need for the discovery of novel antibiotics. This is particularly true for tuberculosis (TB) for which 3.7% of new cases and 20% of previously treated cases are estimated to be caused by multi-drug resistant strains. In addition, in the case of TB, which claimed 1.5 million lives in 2014, the treatment of the least complicated, drug sensitive cases is lengthy and disagreeable. Therefore, new drugs with novel targets are urgently needed to control resistant Mycobacterium tuberculosis strains. In this manuscript we report the characterization of the thiopeptide micrococcin P1 as an anti-tubercular agent. Our biochemical experiments show that this antibiotic inhibits the elongation step of protein synthesis in mycobacteria. We have further identified micrococcin resistant mutations in the ribosomal protein L11 (RplK); the mutations were located in the proline loop at the N-terminus. Reintroduction of the mutations into a clean genetic background, confirmed that they conferred resistance, while introduction of the wild type RplK allele into resistant strains re-established sensitivity. We also identified a mutation in the 23S rRNA gene. These data, in good agreement with previous structural studies suggest that also in M. tuberculosis micrococcin P1 functions by binding to the cleft between the 23S rRNA and the L11 protein loop, thus interfering with the binding of elongation factors Tu and G (EF-Tu and EF-G) and inhibiting protein translocation.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Lungmedicin och allergi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Respiratory Medicine and Allergy (hsv//eng)
Keyword
- Tuberculosis
- Drug development
- Translation
- Thiopeptides
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Degiacomi, Giuli ...
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Personne, Yoann
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Mondesert, Guill ...
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Ge, Xueliang
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Mandava, Chandra ...
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Hartkoorn, Ruben ...
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show more...
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Boldrin, Frances ...
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Goel, Pavitra
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Peisker, Kristin
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Benjak, Andrej
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Barrio, Maria Be ...
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Ventura, Marcell ...
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Brown, Amanda C.
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Leblanc, Veroniq ...
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Bauer, Armin
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Sanyal, Suparna
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Cole, Stewart T.
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Lagrange, Sophie
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Parish, Tanya
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Manganelli, Ricc ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Respiratory Medi ...
- Articles in the publication
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Tuberculosis
- By the university
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Uppsala University