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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.

In Vitro and In Vivo Models of Staphylococcus aureus Endophthalmitis Implicate Specific Nutrients in Ocular Infection