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Updated: Jun 18, 2026

Development and Assessment of Intracellular Infection Models for Staphylococcus aureus
Published on: January 17, 2025
Evaluation of capsular and acapsular strains of S. aureus in an experimental brain abscess model
Nilufer Esen1, Gail Wagoner, Napoleon Philips
1Department of Neurology, Holtom-Garrett Program in Neuroimmunology, University of Michigan Medical School, Ann Arbor, MI 48109, United States. nilufer@med.umich.ed
Abstract:
Brain abscesses are mainly caused by either direct or indirect inoculation of gram positive bacteria including Stapylococcus aureus (S. aureus) or Streptococcus species into the central nervous system. In the present study, we aimed to compare potential changes in brain abscess pathogenesis induced by two different strains of S. aureus, namely the laboratory strain RN6390 and the clinical isolate Reynolds. Although the Reynolds strain was expected to be more resistant to eradication by the host, due to the existence of a polysaccharide capsule, and subsequently to be more virulent, instead we found parenchymal damage and mortality rates to be more prominent following RN6390 infection. In contrast, the Reynolds strain proliferated faster and induced early expression of the chemokine CXCL2, matrix metalloproteinase-9 (MMP-9), and complement 3a and C5. Furthermore, there were early and more abundant infiltration of PMNs, T cells and erythrocyte extravasation in brain abscesses induced by the Reynolds strain. However, several immune parameters were not different between the two strains during the later stages of the disease. These results suggest that capsular S. aureus can modulate innate immunity and complement system activation differently than the acapsular strain RN6390, and the early changes induced by Reynolds strain may have an important impact on survival.
Insights
Staphylococcus aureus (S. aureus) brain abscesses show differing pathogenesis between lab and clinical strains. The acapsular RN6390 strain caused more damage and mortality, while the capsular Reynolds strain induced earlier immune responses.
Area of Science:
- Neuroscience
- Infectious Disease
- Microbiology
Background:
- Brain abscesses are serious central nervous system infections.
- Staphylococcus aureus (S. aureus) is a common causative agent.
- Strain-specific differences in S. aureus pathogenesis are not fully understood.
Purpose of the Study:
- To compare brain abscess pathogenesis induced by two S. aureus strains: laboratory RN6390 and clinical Reynolds.
- To investigate the role of S. aureus capsule in virulence and host immune response.
Main Methods:
- Infection of a host model with RN6390 and Reynolds S. aureus strains.
- Assessment of parenchymal damage, mortality rates, bacterial proliferation, and immune cell infiltration.
- Analysis of chemokine (CXCL2), matrix metalloproteinase-9 (MMP-9), and complement (C3a, C5) expression.
Main Results:
- The acapsular RN6390 strain caused greater parenchymal damage and mortality.
- The capsular Reynolds strain exhibited faster proliferation and induced earlier CXCL2, MMP-9, C3a, and C5 expression.
- Reynolds strain led to earlier and more abundant PMN infiltration, T cell presence, and erythrocyte extravasation.
Conclusions:
- Capsular S. aureus (Reynolds) modulates innate immunity and complement activation differently than acapsular strains (RN6390).
- Early immune changes induced by the Reynolds strain may significantly impact host survival.
- Strain-specific virulence factors influence S. aureus brain abscess development and host response.
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