DuP 721 Resistance in Escherichia Coli Strain E2295 (45-5) Results from the Modification of a Bacterial Translation Component
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Authors
Nittis, Thalia
Issue Date
1993
Type
Thesis
Language
en_US
Keywords
Alternative Title
Abstract
DuP 721, a compound belonging to a new class of synthetic antibacterial
agents, the oxazolidinones, could potentially become an important agent in
controlling infections caused by certain gram positive pathogens, especially
those resistant to antibiotics commonly used in clinical settings. Preliminary
studies indicate that the primary action of DuP 721 is on protein synthesis, but
it is not clear which steps in transcription/translation are affected. The focus
of this project was to determine whether the resistance phenotype generated
in an Escherichia coli strain against DuP 721 resulted from the modification of
an intracellular target or from a defect in the ability of the bacterium to take
up the drug. Cell-free extracts from a DuP 721-sensitive strain and from a
DuP 721-resistant strain were prepared by the method of Zubay (Pratt 1984).
The amount of protein synthesized in each extract in the absence and
presence of antibiotic was determined. [35S] methionine was used as the sole
source of methionine to detect protein synthesis directed by a defined DNA
template. The translation products were also analyzed by SDS polyacrylamide
gel electrophoresis. Results described in this report indicate that cell extracts
prepared from the DuP 721-sensitive strain were translationally less active in
the presence of the antibiotic than extracts from DuP 721-resistant strains.
These data indicate that strain E2295 (45-5) resistance to DuP 721 in vivo is not
due to decreased drug uptake, but to the modification of a target in the
transcription/ translation apparatus normally susceptible to DuP 721.
Biochemical and genetic studies may result in identification of oxazolidinone
mode of action.
With honors.
With honors.
Description
vi, 35 p.
Citation
Publisher
Kalamazoo College
License
U.S. copyright laws protect this material. Commercial use or distribution of this material is not permitted without prior written permission of the copyright holder.