Document Detail


Mechanism of action of the oxazolidinone antibacterial agents.
MedLine Citation:
PMID:  15992144     Owner:  NLM     Status:  PubMed-not-MEDLINE    
Abstract/OtherAbstract:
Oxazolidinones represent a new class of synthetic antibacterial agents active against multiply-resistant Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), penicillin-resistant streptococci and vancomycin-resistant enterococci. Eperezolid and linezolid are two novel analogues, which have respectively completed Phase I and Phase II clinical testing. The lack of cross-resistance between oxazolidinones and other antibiotics supports a novel mechanism of action. Oxazolidinones are protein synthesis inhibitors which target an early step involving the binding of N-formylmethionyl-tRNA to the ribosome. Binding studies demonstrate that these agents interact with the 50S subunit, but not the 30S subunit of the ribosome. Crosslinking experiments provide evidence for an interaction with both the 16S rRNA of the small subunit and the 23S rRNA of the large subunit. Development of resistance in the laboratory is slow, resulting in two independently isolated point mutations at G2447U and G2576U of the 23S rRNA. This review discusses the results of published studies involving oxazolidinone mechanism of action.
Authors:
D Shinabarger
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Expert opinion on investigational drugs     Volume:  8     ISSN:  1744-7658     ISO Abbreviation:  Expert Opin Investig Drugs     Publication Date:  1999 Aug 
Date Detail:
Created Date:  2005-07-04     Completed Date:  2005-07-19     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9434197     Medline TA:  Expert Opin Investig Drugs     Country:  England    
Other Details:
Languages:  eng     Pagination:  1195-202     Citation Subset:  -    
Affiliation:
Pharmacia & Upjohn, 7000 Portage Road, Kalamazoo, Michigan, USA. Dean.L.Shinabarger@am.pnu.com
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