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Updated: Apr 21, 2026
Intravitreal Injection and Quantitation of Infection Parameters in a Mouse Model of Bacterial Endophthalmitis
Published on: February 6, 2021
In vitro and in vivo models of Staphylococcus aureus endophthalmitis implicate specific nutrients in ocular infection
Ama Sadaka1, Kelli Palmer1, Takashi Suzuki1
1Departments of Ophthalmology, and Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts, United States of America; The Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, United States of America; Harvard Microbial Sciences Initiative, Cambridge, Massachusetts, United States of America.
Purpose:
To define global transcriptional responses of Staphylococcus aureus and its codY mutant (CodY is a transcription regulator of virulence and metabolic genes in response to branched-chain amino acids) when growing in bovine aqueous (AH) and vitreous humor (VH) in vitro, and to investigate the impact of codY deletion on S. aureus virulence in a novel murine anterior chamber (AC) infection model.
Methods:
For the in vitro model, differential transcriptomic gene expression of S. aureus and its codY mutant grown in chemically defined medium (CDM), AH, and VH was analyzed. Furthermore, the strains were inoculated into the AC of mice. Changes in bacterial growth, electroretinography and inflammation scores were monitored.
Results:
Bovine AH and VH provide sufficient nutrition for S. aureus growth in vitro. Transcriptome analysis identified 72 unique open reading frames differentially regulated ≥10-fold between CDM, AH, and VH. In the AC model, we found comparable growth of the codY mutant and wild type strains in vivo. Average inflammation scores and retinal function were significantly worse for codY mutant-infected eyes at 24 h post-infection.
Conclusion:
Our in vitro bovine AH and VH models identified likely nutrient sources for S. aureus in the ocular milieu. The in vivo model suggests that control of branched-chain amino acid availability has therapeutic potential in limiting S. aureus endophthalmitis severity.
