Influence of DNA template choice on transcription and inhibition of Escherichia coli RNA polymerase

Antimicrob Agents Chemother. 2012 Aug;56(8):4536-9. doi: 10.1128/AAC.00198-12. Epub 2012 Jun 4.

Abstract

In recent decades, quantitative transcription assays using bacterial RNA polymerase (RNAP) have been performed under widely diverse experimental conditions. We demonstrate that the template choice can influence the inhibitory potency of RNAP inhibitors. Furthermore, we illustrate that the sigma factor (σ(70)) surprisingly increases the transcription efficiency of templates with nonphysiological nonprokaryotic promoters. Our results might be a useful guideline in the early stages of using RNAP for drug discovery.

MeSH terms

  • Aminoglycosides / pharmacology
  • DNA, Bacterial / genetics*
  • DNA-Directed RNA Polymerases / antagonists & inhibitors*
  • DNA-Directed RNA Polymerases / genetics*
  • DNA-Directed RNA Polymerases / metabolism
  • Enzyme Inhibitors / pharmacology*
  • Escherichia coli / drug effects
  • Escherichia coli / enzymology
  • Escherichia coli / genetics*
  • Escherichia coli Proteins / genetics
  • Fidaxomicin
  • Lactones / pharmacology
  • Promoter Regions, Genetic*
  • Sigma Factor / antagonists & inhibitors*
  • Sigma Factor / genetics*
  • Sigma Factor / metabolism
  • Templates, Genetic
  • Transcription, Genetic / drug effects*

Substances

  • Aminoglycosides
  • DNA, Bacterial
  • Enzyme Inhibitors
  • Escherichia coli Proteins
  • Lactones
  • Sigma Factor
  • corallopyronin A
  • myxopyronin A
  • RNA polymerase sigma 70
  • DNA-Directed RNA Polymerases
  • Fidaxomicin