A macrophage-based screen identifies antibacterial compounds selective for intracellular Salmonella Typhimurium

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Updated: Jan 30, 2026

Isolation of Salmonella typhimurium-containing Phagosomes from Macrophages
10:33

Isolation of Salmonella typhimurium-containing Phagosomes from Macrophages

Published on: October 25, 2017

11.2K

Michael J Ellis1,2, Caressa N Tsai1,2, Jarrod W Johnson1,2,3

  • 1Department of Biochemistry and Biomedical Sciences, McMaster University, 1280 Main St W, Hamilton, ON, L8S 4K1, Canada.

Nature Communications
|January 16, 2019
PubMed

Insights

Researchers discovered metergoline, a psychoactive drug, effectively inhibits intracellular Salmonella Typhimurium replication. This novel antimicrobial disrupts bacterial membranes, improving survival in systemic infections.

Area of Science:

  • Microbiology
  • Infectious Diseases
  • Drug Discovery

Background:

  • Salmonella Typhimurium (S. Tm) causes systemic infections by evading immune responses and replicating within host phagocytes.
  • Identifying inhibitors of intracellular bacterial growth is crucial for developing new antimicrobial therapies.

Purpose of the Study:

  • To identify compounds that inhibit intracellular Salmonella Typhimurium replication.
  • To evaluate the antimicrobial activity of metergoline against intracellular S. Tm.

Main Methods:

  • Parallel chemical screens were performed using S. Tm in macrophage-mimicking media and within macrophages.
  • A Salmonella Typhimurium deletion library was screened in the presence of metergoline.
  • Metergoline's mechanism of action was investigated, and its efficacy in a systemic infection model was assessed.

Main Results:

  • Several compounds inhibiting intracellular S. Tm growth were identified.
  • Metergoline demonstrated specific antimicrobial activity against intracellular S. Tm.
  • Outer membrane mutants showed hypersensitivity to metergoline, indicating its disruption of the proton motive force.
  • Metergoline treatment extended animal survival during systemic S. Tm infection.

Conclusions:

  • Intracellular screens can predict in vivo efficacy for antimicrobial drug discovery.
  • Metergoline is a novel antimicrobial agent effective against Salmonella, particularly in the intracellular environment.
  • Metergoline's mechanism involves disrupting the bacterial proton motive force, offering a new therapeutic strategy.

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