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Subcutaneous Infection of Methicillin Resistant Staphylococcus Aureus MRSA
Published on: February 9, 2011
Methicillin resistance in Staphylococcus aureus modulates the transcriptome and disease pathology in a murine model
Poonam Naik1, Milind N Naik2, Dilip K Mishra3
1Jhaveri Microbiology Centre, Brien Holden Eye Research Centre, L. V. Prasad Eye Institute, Telangana, India; Manipal Academy of Higher Education, Karnataka, India.
Abstract:
The ever-increasing incidence of methicillin-resistant strains of Staphylococcus aureus (MRSA) endophthalmitis is of particular concern as they are associated with poor outcomes. To compare the histology and whole transcriptome of Methicillin resistant (MRSA) and Methicillin-susceptible (MSSA) Staphylococcus aureus endophthalmitis in an experimental murine model. MRSA and MSSA endophthalmitis was induced in C57BL/6 mice and disease progression was scored clinically and histologically at 24 h p.i. Retinal changes were monitored by H&E, CD45, MPO and GFAP staining followed by retinal cell death evaluation. Whole Transcriptome was analysed using the SuperPrint G3 Mouse Gene Expression v2 chip. Differential gene expression analysis (Limma package, R) was done followed by enrichment of pathways (KEGG database). Increased corneal haze, diminished vitreous clarity and red reflex was observed in MRSA infected mice eye compared to MSSA (p = 0.04). Histological assessment also corroborated with increased disease severity in MRSA (p = 0.02). Although MRSA infected eye displayed higher CD45+ cells and greater GFAP intensity, the difference was not statistically significant. However, higher retinal cell death was found to be associated with the MRSA infection (p = 0.007). Our study also revealed that MRSA infection induces changes in host transcriptome (FC = 1.5, p = 0.05), revealing the involvement of several interleukins (IL-11,15,10,1ra), chemokines (CCL-11, CXCL-1), Interferon receptors, GM-CSF, M-CSF, MMPs, Neruopilin2 (NRP-2), Ubiquitin associated peptidase and apoptotic ligands. ErbB signalling, JAK-STAT, adipocytokine and Ras signalling were the top divergently enriched pathways. Our study confirms the differential host immune response triggered by MRSA infection in the eye. Our study may help to elucidate the mechanisms of pathogenesis and to identify additional candidate drug targets for the treatment of MRSA endophthalmitis.
Insights
Methicillin-resistant Staphylococcus aureus (MRSA) endophthalmitis causes more severe eye disease than methicillin-susceptible strains. MRSA infection alters the host immune response and transcriptome, offering potential new drug targets.
Area of Science:
- Ophthalmology
- Infectious Diseases
- Immunology
Background:
- Methicillin-resistant Staphylococcus aureus (MRSA) endophthalmitis presents a growing clinical challenge due to poor patient outcomes.
- Understanding the differential host response to MRSA versus methicillin-susceptible S. aureus (MSSA) is crucial for developing effective treatments.
Purpose of the Study:
- To compare the histological and whole transcriptome differences between MRSA and MSSA endophthalmitis in a murine model.
- To identify key host immune pathways and molecular targets involved in MRSA-induced endophthalmitis.
Main Methods:
- Induction of MRSA and MSSA endophthalmitis in C57BL/6 mice.
- Clinical and histological scoring, retinal cell death evaluation, and immunohistochemical staining (H&E, CD45, MPO, GFAP).
- Whole transcriptome analysis using gene expression chips, followed by differential gene expression and pathway enrichment analysis (Limma, KEGG).
Main Results:
- MRSA infection led to significantly increased corneal haze, vitreous opacity, and overall disease severity compared to MSSA.
- Higher retinal cell death was observed in MRSA-infected eyes (p=0.007).
- MRSA infection induced significant changes in host gene expression, implicating interleukins, chemokines, interferon receptors, and signaling pathways like ErbB and JAK-STAT.
Conclusions:
- MRSA endophthalmitis exhibits greater clinical and histological severity than MSSA endophthalmitis in this model.
- MRSA infection triggers a distinct host immune and transcriptional response in the eye.
- The identified pathways and molecules represent potential therapeutic targets for MRSA endophthalmitis treatment.
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