Project 4: The Zebrafish embryo as a model of P. aeruginosa systemic infection
We have developed the optically transparent and genetically tractable zebrafish embryo as a model for systemic P. aeruginosa infection. Despite lacking adaptive immunity at this developmental stage, zebrafish embryos are highly resistant to P. aeruginosa infection, but as in humans, phagocyte depletion dramatically increases their susceptibility.
We have shown that P. aeruginosa lacking a functional Type III secretion system (T3SS) has attenuated virulence, which can be restored through phagocyte depletion. This suggests that the T3SS influences virulence through its effects on phagocytes. Neutrophils and macrophages in zebrafish embryos rapidly phagocytose and kill P. aeruginosa, suggesting that both cell types play a role in protection against infection. Our ongoing work takes advantage of the real-time visualization capabilities and genetic tractability of the zebrafish embryo infection model to elucidate the molecular and cellular details of P. aeruginosa pathogenesis and to explore how the antibiotic resistance of this organism may be induced in vivo.
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