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Niche-Specific Activation of the Oxidative Stress Response by the Pathogenic Fungus Candida albicans

机译：生态位特异性激活的病原真菌白色念珠菌的氧化应激反应。

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Candida albicans is a major opportunistic pathogen of humans. The pathogenicity of this fungus depends upon its ability to deal effectively with the host defenses and, in particular, the oxidative burst of phagocytic cells. We have explored the activation of the oxidative stress response in C. albicans in ex vivo infection models and during systemic infection of a mammalian host. We have generated C. albicans strains that contain specific green fluorescent protein (GFP) promoter fusions and hence act as biosensors of environmental oxidative stress at the single-cell level. Having confirmed that CTA1-, TRX1-, and TTR1/GRX2-GFP reporters respond specifically to oxidative stress, and not to heat shock, nitrosative, or osmotic stresses, we used these reporters to show that individual C. albicans cells activate an oxidative stress response following phagocytosis by neutrophils, but not by macrophages. Significantly, only a small proportion of C. albicans cells (about 4%) activated an oxidative stress response during systemic infection of the mouse kidney. The response of these cells was generally equivalent to exposure to 0.4 mM hydrogen peroxide in vitro. We conclude that most C. albicans cells are exposed to an oxidative stress when they come into contact with neutrophils in the bloodstream of the host but that oxidative killing is no longer a significant threat once an infection has been established in the kidney.
机译：白色念珠菌是人类的主要机会病原体。这种真菌的致病性取决于其有效处理宿主防御的能力，尤其是吞噬细胞的氧化性爆发。我们已经探索了 C中氧化应激反应的激活。在体外感染模型中和哺乳动物宿主的全身感染中。我们生成了 C。含有特定绿色荧光蛋白（GFP）启动子融合体的白色念珠菌菌株，因此在单细胞水平上充当环境氧化应激的生物传感器。确认 CTA1 -， TRX1 -和 TTR1 / GRX2-GFP 报告基因对氧化应激有特异性反应，而对热休克，亚硝化反应没有特异性或渗透压，我们用这些报告者证明了个体 C。白色细胞通过吞噬作用激活嗜中性粒细胞而不是巨噬细胞氧化应激反应。值得注意的是， C仅占很小的比例。白色念珠菌细胞（约4％）在小鼠肾脏的全身感染过程中激活了氧化应激反应。这些细胞的反应通常等同于体外暴露于0.4 mM过氧化氢。我们得出结论，大多数 C。当白色念珠菌细胞与宿主血液中的中性粒细胞接触时，它们会遭受氧化应激，但是一旦在肾脏中建立了感染，氧化杀伤就不再是一个重大威胁。

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