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Published on: May 23, 2021
Identification of a novel Staphylococcus aureus two-component leukotoxin using cell surface proteomics
Christy L Ventura1, Natalia Malachowa, Carl H Hammer
1Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, United States of America.
Researchers discovered a new toxin, LukGH, on the surface of Staphylococcus aureus USA300. This potent leukotoxin attacks human neutrophils, potentially explaining the high virulence of community-associated methicillin-resistant S. aureus (CA-MRSA) infections.
Area of Science:
- Microbiology
- Immunology
- Proteomics
Background:
- Staphylococcus aureus is a major cause of hospital and community infections.
- Community-associated methicillin-resistant S. aureus (CA-MRSA) strains, like USA300, exhibit high virulence, often affecting healthy individuals.
- Understanding the factors contributing to CA-MRSA enhanced virulence is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the cell surface proteome (surfome) of the highly virulent USA300 strain.
- To identify novel extracellular factors contributing to CA-MRSA virulence.
- To characterize a newly identified two-component leukotoxin, LukGH.
Main Methods:
- Proteomic analysis of the USA300 surface proteome using tandem mass spectrometry.
- Identification and quantification of surface-associated proteins.
- Generation of isogenic lukGH deletion strains.
- In vitro assays using human neutrophils to assess pore formation, lysis, and synergistic effects with Panton-Valentine leukocidin (PVL).
Main Results:
- 113 proteins were identified on the USA300 surface, with Protein A being the most abundant.
- A novel two-component leukotoxin, LukGH, was identified as a highly abundant surface-associated protein.
- LukGH demonstrated cytolytic activity against human neutrophils and synergized with PVL to enhance neutrophil lysis.
- LukGH was also found to be secreted into the culture media.
Conclusions:
- LukGH is a novel two-component leukotoxin produced by Staphylococcus aureus USA300.
- LukGH exhibits direct cytolytic activity against human neutrophils.
- This leukotoxin likely contributes to the enhanced virulence of CA-MRSA by targeting immune cells.
