The Transcriptional Response of Cryptococcus neoformans to Ingestion by Acanthamoeba castellanii and Macrophages Provides Insights into the Evolutionary Adaptation to the Mammalian Host
The Transcriptional Response of Cryptococcus neoformans to Ingestion by Acanthamoeba castellanii and Macrophages Provides Insights into the Evolutionary Adaptation to the Mammalian Host
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DOI：
10.1128/ec.00073-13
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发表时间：
2013-05-01
期刊：
影响因子：
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通讯作者：
Casadevall, Arturo
中科院分区：
文献类型：
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作者：
Derengowski, Lorena da S.;Paes, Hugo Costa;Casadevall, Arturo
新生隐球菌对哺乳动物的毒力，特别是它的细胞内风格，被认为是通过原生动物捕食对其自然环境的进化压力而产生的，这促进了允许巨噬细胞内生存的策略的选择。事实上，卡氏棘阿米巴摄取酵母细胞，然后酵母细胞可以在细胞内复制。此外，在哺乳动物宿主中建立感染所需的大多数真菌因子对变形虫内的生存也是重要的。为了更好地了解新生葡萄球菌毒力的来源，我们比较了阿米巴内化的酵母细胞和小鼠巨噬细胞在感染6h后的转录谱。我们的结果显示，656个基因和293个基因的表达分别随着阿米巴和巨噬细胞内环境的变化而变化至少2倍。在这两组发现的基因中，我们重点研究了开放阅读框架CNAG_05662，它可能与糖的运输有关，但没有确定的生物学功能。为了鉴定它的功能，我们构建了一个突变菌株，并评估了它在不同碳源上的生长能力。结果表明，该基因被命名为PTP1(多元醇转运蛋白1)，参与甘露醇和山梨醇等5碳和6碳多元醇的转运，但它的存在与否对隐球菌对小鼠和蛾类幼虫的毒力没有影响。总体而言，这些结果与哺乳动物毒力源于环境中真菌-原生动物相互作用的假设是一致的，并为更好地理解新生隐球菌如何适应哺乳动物宿主提供了更好的理解。
Virulence of Cryptococcus neoformans for mammals, and in particular its intracellular style, was proposed to emerge from evolutionary pressures on its natural environment by protozoan predation, which promoted the selection of strategies that allow intracellular survival in macrophages. In fact, Acanthamoeba castellanii ingests yeast cells, which then can replicate intracellularly. In addition, most fungal factors needed to establish infection in the mammalian host are also important for survival within the amoeba. To better understand the origin of C. neoformans virulence, we compared the transcriptional profile of yeast cells internalized by amoebae and murine macrophages after 6 h of infection. Our results showed 656 and 293 genes whose expression changed at least 2-fold in response to the intracellular environments of amoebae and macrophages, respectively. Among the genes that were found in both groups, we focused on open reading frame (ORF) CNAG_05662, which was potentially related to sugar transport but had no determined biological function. To characterize its function, we constructed a mutant strain and evaluated its ability to grow on various carbon sources. The results showed that this gene, named PTP1 (polyol transporter protein 1), is involved in the transport of 5- and 6-carbon polyols such as mannitol and sorbitol, but its presence or absence had no effect on cryptococcal virulence for mice or moth larvae. Overall, these results are consistent with the hypothesis that the capacity for mammalian virulence originated from fungus- protozoan interactions in the environment and provide a better understanding of how C. neoformans adapts to the mammalian host.