On the target of a novel class of antibiotics, oxazolidinones, active against multidrug-resistant Gram-positive bacteria

FEBS Letters
H BurghardtM Müller

Abstract

Oxazolidinones are a promising new class of synthetic antibiotics active against multidrug-resistant Gram-positive bacteria. To elucidate their mode of action, the effect of DuP 721 on individual steps of protein translation was studied. The drug does not interfere with translation initiation at the stage of mRNA binding or formation of 30S pre-initiation complexes. However, it inhibits the puromycin-mediated release of [35S]formyl-methionine from 70S initiation complexes in a dose-dependent manner. Inhibition involves binding of the oxazolidinone to the large ribosomal subunit and is twice as high with 50S subunits from Gram-positive as with those from Gram-negative bacteria.

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Citations

Jun 22, 2000·Medicinal Research Reviews·Q LiL L Shen
Sep 2, 2008·Proceedings of the National Academy of Sciences of the United States of America·Daniel N WilsonPaola Fucini
Aug 30, 2005·Antimicrobial Agents and Chemotherapy·Eva E NagiecKaren L Leach
Nov 12, 2002·Nihon yakurigaku zasshi. Folia pharmacologica Japonica·Kazuhiko IrinodaMunehiro Hashimoto
Dec 29, 2005·Proceedings of the National Academy of Sciences of the United States of America·Letizia BrandiClaudio O Gualerzi
Nov 26, 2009·Critical Reviews in Biochemistry and Molecular Biology·Daniel N Wilson
May 5, 2001·Expert Opinion on Pharmacotherapy·R Norrby
Jul 5, 2005·Expert Opinion on Investigational Drugs·D Shinabarger
Aug 3, 2001·The Journal of Biological Chemistry·U PatelE V Bobkova
Mar 21, 2003·The Journal of Biological Chemistry·Ekaterina V BobkovaDavid L Pompliano
Apr 12, 2003·The Journal of Biological Chemistry·Jerry R ColcaAlexander S Mankin
Dec 3, 1998·Antimicrobial Agents and Chemotherapy·S M SwaneyD L Shinabarger

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