Staphylococcus aureus α-toxin-dependent induction of host cell death by membrane-derived vesicles

Bernard Thay1, Sun Nyunt Wai, Jan Oscarsson

  • 1Oral Microbiology, Department of Odontology, Umeå University, Umeå, Sweden.

Plos One
|February 6, 2013
PubMed

Insights

Staphylococcus aureus releases membrane vesicles (MVs) that deliver alpha-toxin (Hla) to human cells. This toxin, carried by MVs, is crucial for S. aureus cytotoxicity and infection progression.

Area of Science:

  • Microbiology
  • Cell Biology
  • Infectious Diseases

Background:

  • Staphylococcus aureus causes diverse human infections.
  • Gram-positive bacteria, including S. aureus, release membrane-derived vesicles (MVs).
  • MVs may deliver virulence factors to host cells, similar to Gram-negative outer membrane vesicles (OMVs).

Purpose of the Study:

  • To investigate the role of S. aureus MVs in delivering virulence factors.
  • To determine if MVs mediate the delivery of alpha-toxin (Hla) to human cells.
  • To assess the contribution of Hla within MVs to S. aureus-induced cytotoxicity.

Main Methods:

  • Isolation of membrane-derived vesicles (MVs) from Staphylococcus aureus.
  • Characterization of alpha-toxin (Hla) association with MVs.
  • Assessment of MV-mediated cytotoxicity on HeLa cells and erythrocytes.
  • Comparison of MVs from wild-type and isogenic hla mutant strains.

Main Results:

  • Biologically active alpha-toxin (Hla) was tightly associated with S. aureus MVs.
  • S. aureus MVs exhibited cytotoxicity towards HeLa cells, primarily mediated by Hla.
  • Hla within MVs was responsible for the majority of erythrocyte lysis.
  • MVs from an hla mutant strain showed significantly reduced cytotoxicity.

Conclusions:

  • Cholesterol-dependent fusion of S. aureus MVs with host cell membranes facilitates Hla delivery.
  • S. aureus MVs are key vehicles for delivering the pore-forming toxin Hla.
  • This study identifies Hla as a major MV-associated factor contributing to S. aureus host cell cytotoxicity.

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