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Updated: Mar 8, 2026

Purification of Pathogen Vacuoles from Legionella-infected Phagocytes
09:25

Purification of Pathogen Vacuoles from Legionella-infected Phagocytes

Published on: June 19, 2012

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Acyl Histidines: New N-Acyl Amides from Legionella pneumophila

Thomas Tørring1, Stephanie R Shames2, Wooyoung Cho3,4

  • 1Interdiscplinary Nanoscience Center, Aarhus University, Gustav Wieds Vej 14, 8000, Aarhus C, Denmark.

Chembiochem : a European Journal of Chemical Biology
|January 25, 2017
PubMed

Insights

Legionella pneumophila produces novel metabolites from an orphan gene cluster. These compounds, including N-acyl-l-histidine derivatives, impact bacterial growth within host cells, offering new insights into pathogen virulence.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Biochemistry

Background:

  • Legionella pneumophila is a Gram-negative bacterium causing Legionnaires' disease.
  • It replicates intracellularly in human macrophages and protozoa.
  • L. pneumophila possesses an orphan biosynthetic gene cluster (BGC) with isocyanide-related genes, upregulated during infection.

Purpose of the Study:

  • To characterize metabolites produced by the orphan BGC in L. pneumophila.
  • To investigate the role of these metabolites in intracellular replication within amoeba and macrophages.

Main Methods:

  • Pathway-targeted molecular networking was employed to identify metabolites.
  • Tetrazine-based chemoselective ligation chemistry was used for metabolite characterization.
  • Intracellular growth assays were performed in amoeba and murine bone-marrow-derived macrophages.

Main Results:

  • Two distinct groups of aromatic amino acid-derived metabolites were identified.
  • A known tyrosine-derived isocyanide and a family of novel N-acyl-l-histidine metabolites were discovered.
  • These metabolites were assessed for their contribution to intracellular growth.

Conclusions:

  • The orphan BGC in L. pneumophila produces diverse metabolites, including novel N-acyl-l-histidines.
  • These findings expand our understanding of Legionella's metabolic capabilities and potential virulence factors.
  • Further research is warranted to elucidate the precise roles of these metabolites in host-pathogen interactions.
Keywords:
legionellosismetabolomicsnatural productpneumoniasecondary metabolism

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