Polyphosphate uses mTOR, pyrophosphate, and Rho GTPase components to potentiate bacterial survival in Dictyostelium

Ryan J Rahman1, Ramesh Rijal1, Shiyu Jing1

  • 1Department of Biology, Texas A&M University , College Station, Texas, USA.

Mbio
|September 27, 2023
PubMed
Abstract

Insights

Pathogenic bacteria like Mycobacterium use polyphosphate (polyP) to evade immune cells. Researchers identified a polyP-sensing pathway in Dictyostelium discoideum, crucial for bacterial survival, with potential therapeutic implications for human macrophages.

Area of Science:

  • Cellular microbiology
  • Signal transduction
  • Host-pathogen interactions

Background:

  • Most bacteria are rapidly eliminated by phagocytosis within eukaryotic cells.
  • Certain pathogenic bacteria, including Mycobacterium species, survive phagocytosis by secreting polyphosphate (polyP).
  • Exogenous polyP inhibits the killing of bacteria by human macrophages and Dictyostelium discoideum.

Purpose of the Study:

  • To identify the key components of the polyphosphate (polyP) signal transduction pathway in Dictyostelium discoideum.
  • To investigate the role of this pathway in preventing the killing of ingested bacteria.
  • To explore the potential therapeutic applications of targeting this pathway in human macrophages.

Main Methods:

  • Genetic screening to identify components of the polyP signal transduction pathway in Dictyostelium discoideum.
  • Phagocytosis assays using wild-type and mutant Dictyostelium discoideum strains.
  • Comparative analysis of pathway component orthologs in human cells.

Main Results:

  • Key components of the polyP signal transduction pathway in Dictyostelium discoideum were identified.
  • In Dictyostelium discoideum cells lacking these components, polyP failed to inhibit the killing of ingested bacteria.
  • Orthologs of these pathway components exist in human cells.

Conclusions:

  • A novel polyP signal transduction pathway is essential for pathogenic bacteria to evade killing by Dictyostelium discoideum.
  • This pathway's conservation in humans suggests a potential therapeutic target for treating infections caused by intracellular pathogens.
  • Pharmacological inhibition of this pathway in human macrophages could enhance their ability to eliminate pathogens like Mycobacterium tuberculosis.

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