Intraphagolysosomal conditions predispose to Staphylococcus epidermidis small colony variants persistence in

Agnieszka Magryś1, Kamil Deryło2, Agnieszka Bogut1

  • 1Chair and Department of Medical Microbiology, Medical University of Lublin, Lublin, Poland.

Plos One
|November 10, 2018
PubMed

Insights

Staphylococcus epidermidis small colony variants (SCV) persist within macrophages, aided by phagosomal acidification. Interferon-gamma (IFN-γ) effectively kills SCV by alkalizing phagosomes and increasing iNOS synthesis, controlling infection.

Area of Science:

  • Microbiology
  • Immunology
  • Cell Biology

Background:

  • Staphylococcus epidermidis small colony variants (SCV) are implicated in persistent biomaterial-associated infections.
  • SCV's ability to survive intracellularly within macrophages is a key factor in pathogenesis.
  • Understanding SCV-macrophage interactions is crucial for developing effective treatment strategies.

Purpose of the Study:

  • To determine the intracellular location of S. epidermidis SCV and wild-type (WT) strains within macrophages.
  • To investigate the effects of IFN-γ and rapamycin on SCV/WT intracellular survival, lysosome colocalization, and iNOS induction.
  • To elucidate the mechanisms by which IFN-γ controls S. epidermidis SCV infection.

Main Methods:

  • Intracellular localization of S. epidermidis SCV and WT strains in macrophages.
  • Assessment of phagosomal acidification using LysoTracker.
  • Measurement of inducible nitric oxide synthase (iNOS) induction.
  • Treatment with IFN-γ and rapamycin in THP-activated macrophages.

Main Results:

  • SCV survive and persist within macrophages, supported by phagosomal acidification.
  • IFN-γ treatment reduced LysoTracker-positive SCV-containing phagosomes, indicating SCV killing.
  • IFN-γ mediated SCV killing through phagosome alkalization and increased iNOS synthesis.
  • SCV were less potent iNOS inducers than WT strains, potentially aiding persistence.
  • Rapamycin reduced bacterial presence in acidic organelles but did not affect iNOS synthesis.

Conclusions:

  • IFN-γ effectively controls S. epidermidis WT and SCV infections in macrophages via distinct killing mechanisms.
  • SCV possess unique metabolic adaptations enabling survival within the hostile macrophage environment.
  • Targeting SCV intracellular survival mechanisms may offer new therapeutic avenues for biomaterial-associated infections.

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