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Published on: July 17, 2013
Direct and synergistic hemolysis caused by Staphylococcus phenol-soluble modulins: implications for diagnosis and
Gordon Y C Cheung1, Anthony C Duong, Michael Otto
1Pathogen Molecular Genetics Section, Laboratory of Human Bacterial Pathogenesis, National Institute of Allergy and Infectious Diseases, The National Institutes of Health, Bethesda, MD 20892, USA.
Abstract:
Phenol-soluble modulins are secreted staphylococcal peptides with an amphipathic α-helical structure. Some PSMs are strongly cytolytic toward human neutrophils and represent major virulence determinants during Staphylococcus aureus skin and blood infection. However, capacities of PSMs to lyse human erythrocytes have not been investigated. Here, we demonstrate that many S. aureus and Staphylococcus epidermidis PSMs lyse human erythrocytes. Furthermore, synergism with S. aureus β-toxin considerably increased the hemolytic capacities of several PSMs. This synergism may be of key importance in PSM and β-toxin-producing S. aureus or in mixed-strain or -species infections with PSM and β-toxin producers. Of specific interest, several PSMs, in particular PSMα peptides, contributed to a considerable extent to synergistic hemolysis with β-toxin or when using the β-toxin-producing strain RN4220 in CAMP assays. Thus, CAMP-type assays should not be used to detect or quantify S. aureus δ-toxin production, but may be used for an overall assessment of Agr functionality. Our study suggests an additional role of PSMs in staphylococcal pathogenesis and demonstrates that the repertoire of staphylococcal hemolysins is not limited to S. aureus and is much larger and diverse than previously thought.
Insights
Phenol-soluble modulin (PSM) peptides from Staphylococcus species lyse human red blood cells. Their hemolytic activity is enhanced by β-toxin, suggesting a broader role in staphylococcal infections.
Area of Science:
- Microbiology
- Molecular Biology
- Pathogenesis
Background:
- Phenol-soluble modulins (PSMs) are amphipathic α-helical peptides secreted by staphylococci.
- Certain PSMs are potent cytolysins against human neutrophils, acting as key virulence factors in Staphylococcus aureus infections.
- The hemolytic potential of PSMs against human erythrocytes remains largely unexplored.
Purpose of the Study:
- To investigate the capacity of PSMs from S. aureus and Staphylococcus epidermidis to lyse human erythrocytes.
- To determine if PSMs exhibit synergistic hemolytic activity with S. aureus β-toxin.
- To elucidate the role of PSMs in staphylococcal pathogenesis and hemolysin diversity.
Main Methods:
- Erythrolysis assays using purified PSMs from S. aureus and S. epidermidis.
- Assessment of synergistic hemolysis between PSMs and purified S. aureus β-toxin.
- CAMP assays utilizing the β-toxin-producing S. aureus strain RN4220.
Main Results:
- Many S. aureus and S. epidermidis PSMs were found to lyse human erythrocytes.
- Synergistic interactions between several PSMs and S. aureus β-toxin significantly enhanced hemolytic activity.
- PSMα peptides, in particular, demonstrated substantial contribution to synergistic hemolysis.
- CAMP assays indicated PSMs' role in synergistic hemolysis, not suitable for δ-toxin detection but useful for Agr functionality assessment.
Conclusions:
- PSMs possess hemolytic activity against human erythrocytes, expanding their known pathogenic roles.
- Synergism between PSMs and β-toxin is a significant factor in staphylococcal virulence, especially in mixed infections.
- The diversity of staphylococcal hemolysins is greater than previously understood, with PSMs contributing significantly.
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