Lipoyl-E2-PDH Gets a Second Job

Seth W Dickey1, Michael Otto1

  • 1Pathogen Molecular Genetics Section, Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, U.S. National Institutes of Health, Bethesda, MD, USA.

Cell Host & Microbe
|November 10, 2017
PubMed

Insights

Staphylococcus aureus secretes a component of the pyruvate dehydrogenase (PDH) complex. This secreted component suppresses host immune responses, specifically the activation of macrophages by bacterial lipoproteins.

Area of Science:

  • Microbiology
  • Immunology
  • Metabolic pathways

Background:

  • Pyruvate dehydrogenase (PDH) is a key enzyme complex in cellular metabolism.
  • Bacterial lipoproteins are known triggers of host immune responses via Toll-like receptors (TLRs).

Purpose of the Study:

  • To investigate the role of secreted bacterial factors in modulating host immune responses.
  • To determine the function of the pyruvate dehydrogenase complex in the context of Staphylococcus aureus infection.

Main Methods:

  • Analysis of secreted proteins from Staphylococcus aureus.
  • Investigating the interaction of bacterial lipoproteins with host immune cells.
  • Assessing the impact of pyruvate dehydrogenase components on TLR signaling.

Main Results:

  • Staphylococcus aureus secretes the lipoylated E2 subunit of the PDH complex.
  • This secreted E2 subunit suppresses TLR-mediated activation of host macrophages.
  • The bacterial PDH E2 subunit interferes with immune signaling pathways triggered by lipoproteins.

Conclusions:

  • The bacterial pathogen Staphylococcus aureus utilizes a metabolic enzyme component for immune evasion.
  • Secretion and repurposing of the PDH E2 subunit represent a novel mechanism for suppressing host immunity.

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