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首页> 外文期刊>Infection and immunity >The Candida albicans ATO Gene Family Promotes Neutralization of the Macrophage Phagolysosome
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The Candida albicans ATO Gene Family Promotes Neutralization of the Macrophage Phagolysosome

机译：白色念珠菌ATO基因家族促进巨噬细胞吞噬体的中和。

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Candida albicans is an opportunistic human fungal pathogen that causes a variety of diseases, ranging from superficial mucosal to life-threatening systemic infections, the latter particularly in patients with defects in innate immune function. C. albicans cells phagocytosed by macrophages undergo a dramatic change in their metabolism in which amino acids are a key nutrient. We have shown that amino acid catabolism allows the cell to neutralize the phagolysosome and initiate hyphal growth. We show here that members of the 10-gene ATO family, which are induced by phagocytosis or the presence of amino acids in an Stp2-dependent manner and encode putative acetate or ammonia transporters, are important effectors of this pH change in vitro and in macrophages. When grown with amino acids as the sole carbon source, the deletion of ATO5 or the expression of a dominant-negative ATO1G53D allele results in a delay in alkalinization, a defect in hyphal formation, and a reduction in the amount of ammonia released from the cell. These strains also form fewer hyphae after phagocytosis, have a reduced ability to escape macrophages, and reside in more acidic phagolysosomal compartments than wild-type cells. Furthermore, overexpression of many of the 10 ATO genes accelerates ammonia release, and an ato5Δ ATO1G53D double mutant strain has additive alkalinization and ammonia release defects. Taken together, these results indicate that the Ato protein family is a key mediator of the metabolic changes that allow C. albicans to overcome the macrophage innate immunity barrier.
机译：白色念珠菌是一种机会性人类真菌病原体，可引起多种疾病，从表层粘膜到威胁生命的全身感染，后者尤其是先天免疫功能缺陷的患者。被巨噬细胞吞噬的白色念珠菌细胞的新陈代谢发生巨大变化，其中氨基酸是关键营养素。我们已经表明，氨基酸分解代谢使细胞能够中和吞噬体并启动菌丝生长。我们在这里显示10基因 ATO 家族的成员，这是由吞噬作用或氨基酸以Stp2依赖的方式诱导并编码假定的乙酸盐或氨转运蛋白而诱导的，是此的重要效应子体外和巨噬细胞的pH值变化。当以氨基酸作为唯一碳源生长时， ATO5 的缺失或显性负 ATO1 G53D <等位基因导致碱化延迟，菌丝形成缺陷以及从细胞释放的氨量减少。与野生型细胞相比，这些菌株在吞噬作用后还形成较少的菌丝，逃避巨噬细胞的能力降低，并位于更多的酸性吞噬溶酶体区室。此外，10个 ATO 基因中的许多基因的过表达会加速氨的释放，而ato5ΔATO1 G53D 双突变株具有添加剂碱化和氨释放缺陷。综上所述，这些结果表明Ato蛋白家族是代谢变化的关键介质，其使白色念珠菌克服了巨噬细胞的固有免疫屏障。

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