Stable albicidin resistance in Escherichia coli involves an altered outer-membrane nucleoside uptake system

Birch, Robert G. and Pemberton, John M. (1990) Stable albicidin resistance in Escherichia coli involves an altered outer-membrane nucleoside uptake system. Journal of General Microbiology, 136 1: 51-58.

Author Birch, Robert G.
Pemberton, John M.
Title Stable albicidin resistance in Escherichia coli involves an altered outer-membrane nucleoside uptake system
Journal name Journal of General Microbiology   Check publisher's open access policy
ISSN 0022-1287
Publication date 1990
Sub-type Article (original research)
Volume 136
Issue 1
Start page 51
End page 58
Total pages 7
Place of publication Reading, Berks, United Kingdom
Publisher Society for General Microbiology
Collection year 1990
Language eng
Subject 270300 Microbiology
Formatted abstract
Albicidin blocked DNA synthesis in intact cells of a PolA- EndA- Escherichia coli strain, and in permeabilized cells supplied with all necessary precursor nucleotides, indicating a direct effect on prokaryote DNA replication. Replication of phages T4 and T7 was also blocked by albicidin in albicidin-sensitive (Alb(s)) but not in albicidin-resistant (Alb(r)) E. coli host-cells. All stable spontaneous Alb(r) mutants of E. coli simultaneously became resistant to phage T6. The locus determining albicidin sensitivity mapped at tsx, the structural gene for an outer-membrane protein used as a receptor by phage T6 and involved in transport through the outer membrane of nucleosides present at submicromolar extracellular concentrations. Albicidin does not closely resemble a nucleoside in structure. However, Alb(s) E. coli strains rapidly accumulated both nucleosides and albicidin from the surrounding medium whereas the Alb(r) mutants were defective in uptake of nucleosides and albicidin at low extracellular concentrations. An insertion mutation blocking Tsx protein production also blocked albicidin uptake and conveyed albicidin resistance. Albicidin supplied at approximately 0.1 μM blocked DNA replication within seconds in intact Alb(s) E. coli cells, but a 100-fold higher albicidin concentration was necessary for a rapid inhibition of DNA replication in permeabilized cells. We conclude that albicidin is effective at very low concentrations against E. coli because it is rapidly concentrated within cells by illicit transport through the tsx-encoded outer-membrane channel normally involved in nucleoside uptake. Albicidin resistance results from loss of the mechanism of albicidin transport through the outer membrane
Keyword Albicidin
Nucleoside
Unclassified drug
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Agriculture and Food Sciences
 
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