Zebrafish are Resistant to Staphylococcus aureus Endophthalmitis

Abstract

Gram-positive bacteria remain the leading cause of endophthalmitis, a blinding infectious disease of the eye. Murine models have been widely used for understanding the pathogenesis of bacterial endophthalmitis. In this study, we sought to develop an alternative zebrafish (Danio rerio) model for Staphylococcus aureus and compare the disease pathobiology to a murine model. Endophthalmitis was induced in zebrafish and C57BL/6 mice through the intravitreal injection of S. aureus. Disease progression was monitored by assessing corneal haze, opacity, bacterial burden, and retinal histology. Our results demonstrated that, unlike the murine models, zebrafish maintained ocular integrity, corneal transparency, and retinal architecture. We found that the zebrafish was capable of clearing S. aureus from the eye via transport through retinal vessels and the optic nerve and by mounting a monocyte/macrophage response beginning at 8 hour post-infection (hpi). The bacterial burden increased up to 8 hpi and significantly decreased thereafter. An assessment of the innate retinal response revealed the induced expression of Il-1β and Il-6 transcripts. Collectively, our study shows that unlike the murine model, zebrafish do not develop endophthalmitis and rapidly clear the pathogen. Hence, a better understanding of the zebrafish protective ocular innate response may provide new insights into the pathobiology of bacterial endophthalmitis.

Staphylococcus aureus Vaccine Research and Development: The Past, Present and Future, Including Novel Therapeutic Strategies

“…The benefits of using this more distantly related organism include: i) the ability to study innate immune responses before the adaptive immune system has developed (this only occurs four weeks after fertilization), ii) a high degree of evolutionary divergence between human and Zebrafish immune systems allows us to specifically examine the functionality of highly conserved genomic material, thereby reducing the complexity of the system in question and iii) advanced microscopy techniques are applicable to this model due to its transparent appearance ( 115 ). Indeed, while utilized significantly less than the mouse model, some important basic research findings concerning the pathogenicity of S. aureus as well as inferences of protective immunity were made using the Zebrafish model ( 116 , 117 ).…”