Nutrient Stress Small-Molecule Screening Platform for Escherichia coli

  • Sara S. El Zahed
  • Garima Kumar
  • Madeline Tong
  • Eric D. Brown
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1787)

Abstract

Clinically approved antibiotics target a narrow spectrum of cellular processes, namely cell wall synthesis, DNA replication, and protein synthesis. Numerous screens have been designed to identify inhibitors that target one of these cellular processes. Indeed, this narrow range of drug mechanisms and a reliance on chemical classes discovered many decades ago are thought to be principally responsible for the current crisis of antibiotic drug resistance. Seeking to expand the target base of antibacterial drug discovery, we developed a nutrient stress screening platform that identifies inhibitors of the growth of in Escherichia coli under nutrient limitation. Under nutrient stress, bacteria require an expanded biosynthetic capacity that includes the synthesis of amino acids, vitamins, and nucleobases. Growing evidence suggests that these processes may be indispensable to certain pathogens and at particular sites of infection. Indeed, more than 100 biosynthetic enzymes become indispensable to E. coli grown under nutrient stress in vitro. The screening platform described here puts a focus on these novel targets for new antibiotics and prioritizes growth inhibitory compounds that can be suppressed by individual nutrients and pools thereof.

Key words

Antibacterials Nutrient stress Growth inhibition 

Notes

Acknowledgments

This research was supported by an operating grant from the Canadian Institutes for Health Research (FDN-143215), a Leaders Opportunity Fund grant from the Canada Foundation for Innovation, and a Tier I Canada Research Chair award to E.D.B.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Sara S. El Zahed
    • 1
    • 2
  • Garima Kumar
    • 1
    • 2
  • Madeline Tong
    • 1
    • 2
  • Eric D. Brown
    • 1
    • 2
  1. 1.Department of Biochemistry and Biomedical SciencesMcMaster UniversityHamiltonCanada
  2. 2.Michael G. DeGroote Institute for Infectious Disease ResearchMcMaster UniversityHamiltonCanada

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