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Updated: Oct 17, 2025
Quantifying the Cytotoxicity of Staphylococcus aureus Against Human Polymorphonuclear Leukocytes
Published on: January 3, 2020
The MpsB protein contributes to both the toxicity and immune evasion capacity of Staphylococcus aureus
Edward J A Douglas1, Seána Duggan1, Tarcisio Brignoli1
1School of Cellular and Molecular Medicine, University of Bristol, Bristol, BS8 1TD, UK.
Abstract:
Understanding the role specific bacterial factors play in the development of severe disease in humans is critical if new approaches to tackle such infections are to be developed. In this study we focus on genes we have found to be associated with patient outcome following bacteraemia caused by the major human pathogen Staphylococcus aureus. By examining the contribution these genes make to the ability of the bacteria to survive exposure to the antibacterial factors found in serum, we identify three novel serum resistance-associated genes, mdeA, mpsB and yycH. Detailed analysis of an MpsB mutant supports its previous association with the slow growing small colony variant (SCV) phenotype of S. aureus, and we demonstrate that the effect this mutation has on membrane potential prevents the activation of the Agr quorum sensing system, and as a consequence the mutant bacteria do not produce cytolytic toxins. Given the importance of both toxin production and immune evasion for the ability of S. aureus to cause disease, we believe that these findings explain the role of the mpsB gene as a mortality-associated locus during human disease.
Insights
Researchers identified three novel genes, mdeA, mpsB, and yycH, that help Staphylococcus aureus survive in human serum. The mpsB gene
Area of Science:
- Bacteriology
- Molecular Biology
- Infectious Diseases
Background:
- Severe Staphylococcus aureus infections pose a significant threat.
- Understanding bacterial virulence factors is key to developing new treatments.
- Specific genes influencing patient outcomes in S. aureus bacteremia require investigation.
Purpose of the Study:
- To identify novel bacterial genes associated with patient outcomes in Staphylococcus aureus bacteremia.
- To investigate the role of these genes in bacterial survival against host immune factors, specifically serum.
Main Methods:
- Analysis of Staphylococcus aureus genes linked to patient outcomes.
- Experimental assessment of bacterial survival in human serum.
- Characterization of a specific mutant (MpsB) for its impact on bacterial phenotype and virulence pathways.
Main Results:
- Three novel serum resistance-associated genes (mdeA, mpsB, yycH) were identified.
- A mutation in mpsB was linked to the small colony variant (SCV) phenotype.
- The mpsB mutation disrupted membrane potential, inhibiting the Agr quorum sensing system and toxin production.
Conclusions:
- The identified genes, particularly mpsB, play a crucial role in Staphylococcus aureus pathogenesis.
- The mpsB gene's association with reduced toxin production and immune evasion explains its role as a mortality-associated factor in human disease.
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