Quick Search:

uzh logo
Browse by:
bullet
bullet
bullet
bullet

Zurich Open Repository and Archive 

Long, K S; Munck, C; Andersen, T B M; Schaub, M A; Hobbie, S N; Böttger, E C; Vester, B (2010). Mutations in 23S rRNA at the peptidyl transferase center and their relationship to linezolid binding and cross-resistance. Antimicrobial Agents and Chemotherapy, 54(11):4705-4713.

Full text not available from this repository.

Abstract

The oxazolidinone antibiotic linezolid targets the peptidyl transferase center (PTC) on the bacterial ribosome. Thirteen single and four double 23S rRNA mutations were introduced into a Mycobacterium smegmatis strain with a single rRNA operon. Converting bacterial base identity by single mutations at positions 2032, 2453, and 2499 to human cytosolic base identity did not confer significantly reduced susceptibility to linezolid. The largest decrease in linezolid susceptibility for any of the introduced single mutations was observed with the G2576U mutation at a position that is 7.9 Å from linezolid. Smaller decreases were observed with the A2503G, U2504G, and G2505A mutations at nucleotides proximal to linezolid, showing that the degree of resistance conferred is not simply inversely proportional to the nucleotide-drug distance. The double mutations G2032A-C2499A, G2032A-U2504G, C2055A-U2504G, and C2055A-A2572U had remarkable synergistic effects on linezolid resistance relative to the effects of the corresponding single mutations. This study emphasizes that effects of rRNA mutations at the PTC are organism dependent. Moreover, the data show a nonpredictable cross-resistance pattern between linezolid, chloramphenicol, clindamycin, and valnemulin. The data underscore the significance of mutations at distal nucleotides, either alone or in combination with other mutated nucleotides, in contributing to linezolid resistance.

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Medical Microbiology
DDC:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2010
Deposited On:24 Jan 2011 14:36
Last Modified:27 Nov 2013 20:59
Publisher:American Society for Microbiology
ISSN:0066-4804
Publisher DOI:10.1128/AAC.00644-10
PubMed ID:20696869
Citations:Web of Science®. Times Cited: 10
Google Scholar™
Scopus®. Citation Count: 11

Users (please log in): suggest update or correction for this item

Repository Staff Only: item control page