Transcriptional response of Candida albicans upon internalization by macrophages
Transcriptional response of Candida albicans upon internalization by macrophages
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DOI：
10.1128/ec.3.5.1076-1087.2004
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发表时间：
2004-10-01
期刊：
影响因子：
--
通讯作者：
Fink, GR
中科院分区：
文献类型：
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作者：
Lorenz, MC;Bender, JA;Fink, GR
条件致病菌白色念珠菌是一种良性肠道共生菌，也是一种经常致命的全身性致病菌。白念珠菌与宿主先天免疫系统的相互作用是这种平衡的主要因素；先天免疫缺陷使患者易患播散性念珠菌病。由于吞噬细胞在抵御真菌感染中的核心重要性，我们利用基因组转录谱研究了白色念珠菌对哺乳动物巨噬细胞吞噬作用的反应。这一分析揭示了白色念珠菌转录的戏剧性重新编程，它发生在两个连续的步骤中。在早期阶段，细胞转变为饥饿模式，包括糖异生生长、激活脂肪酸降解和下调翻译。在较后的阶段，由于菌丝生长使白色念珠菌能够从巨噬细胞中逃逸，细胞迅速恢复糖酵解生长。此外，在早期阶段还嵌入了大量的非代谢反应，包括DNA损伤修复机制、氧化应激反应、肽摄取系统和精氨酸生物合成。此外，令人惊讶的是，对巨噬细胞接触做出反应的基因中有令人惊讶的比例没有已知的同源基因，这表明有机体已经经历了对共生或病原体生活方式的实质性进化适应。这种转录重编程在相关但非致病的酿酒酵母中几乎完全缺失，这表明这些大规模和协调的变化对这种生物在体内生存和致病的能力有很大贡献。
The opportunistic fungal pathogen Candida albicans is both a benign gut commensal and a frequently fatal systemic pathogen. The interaction of C. albicans with the host's innate immune system is the primary factor in this balance; defects in innate immunity predispose the patient to disseminated candidiasis. Because of the central importance of phagocytic cells in defense against fungal infections, we have investigated the response of C. albicans to phagocytosis by mammalian macrophages using genomic transcript profiling. This analysis reveals a dramatic reprogramming of transcription in C. albicans that occurs in two successive steps. In the early phase cells shift to a starvation mode, including gluconeogenic growth, activation of fatty acid degradation, and downregulation of translation. In a later phase, as hyphal growth enables C. albicans to escape from the macrophage, cells quickly resume glycolytic growth. In addition, there is a substantial nonmetabolic response imbedded in the early phase, including machinery for DNA damage repair, oxidative stress responses, peptide uptake systems, and arginine biosynthesis. Further, a surprising percentage of the genes that respond specifically to macrophage contact have no known homologs, suggesting that the organism has undergone substantial evolutionary adaptations to the commensal or pathogen lifestyle. This transcriptional reprogramming is almost wholly absent in the related, but nonpathogenic, yeast Saccharomyces cerevisiae, suggesting that these large-scale and coordinated changes contribute significantly to the ability of this organism to survive and cause disease in vivo.