Identification and analysis of novel small molecule inhibitors of RNase E: implications for antibacterial targeting and regulation of RNase E

Charlotte E. Mardle, Layla Goddard, Bailei Claude Spelman, Helen S. Atkins, Louise Butt, Paul Cox, Darren Gowers, Helen Vincent, Anastasia Callaghan

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Abstract

Increasing resistance of bacteria to antibiotics is a serious global challenge and there is a need to unlock the potential of novel antibacterial targets. One such target is the essential prokaryotic endoribonuclease RNase E. Using a combination of in silico high-throughput screening and in vitro validation we have identified three novel small molecule inhibitors of RNase E that are active against RNase E from Escherichia coli, Francisella tularensis and Acinetobacter baumannii. Two of the inhibitors are non-natural small molecules that could be suitable as lead compounds for the development of broad-spectrum antibiotics targeting RNase E. The third small molecule inhibitor is glucosamine-6-phosphate, a precursor of bacterial cell envelope peptidoglycans and
lipopolysaccharides, hinting at a novel metabolite-mediated mechanism of regulation of RNase E.
Original languageEnglish
Article number100773
JournalBiochemistry and Biophysics Reports
Volume23
Early online date9 Jun 2020
DOIs
Publication statusEarly online - 9 Jun 2020

Keywords

  • RCUK
  • BBSRC
  • BB/J016179/1

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