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Updated: May 14, 2026

Quantifying the Cytotoxicity of Staphylococcus aureus Against Human Polymorphonuclear Leukocytes
Published on: January 3, 2020
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.
Abstract:
Staphylococcus aureus causes a wide spectrum of infections in humans, ranging from superficial cutaneous infections, infections in the circum-oral region, to life-threatening bacteremia. It was recently demonstrated that Gram-positive organisms such as S. aureus liberate membrane-derived vesicles (MVs), which analogously to outer membrane vesicles (OMVs) of Gram-negative bacteria can play a role in delivering virulence factors to host cells. In the present study we have shown that cholesterol-dependent fusion of S. aureus MVs with the plasma membrane represents a route for delivery of a key virulence factor, α-toxin (α-hemolysin; Hla) to human cells. Most S. aureus strains produce this 33-kDa pore-forming protein, which can lyse a wide range of human cells, and induce apoptosis in T-lymphocytes. Our results revealed a tight association of biologically active α-toxin with membrane-derived vesicles isolated from S. aureus strain 8325-4. Concomitantly, α-toxin contributed to HeLa cell cytotoxicity of MVs, and was the main vesicle-associated protein responsible for erythrocyte lysis. In contrast, MVs obtained from an isogenic hla mutant were significantly attenuated with regards to both causing lysis of erythrocytes and death of HeLa cells. This is to our knowledge the first recognition of an S. aureus MV-associated factor contributing to host cell cytotoxicity.
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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