Identification of Cryptococcus neoformans temperature-regulated genes with a genomic-DNA microarray
Identification of Cryptococcus neoformans temperature-regulated genes with a genomic-DNA microarray
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DOI：
10.1128/ec.3.5.1249-1260.2004
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发表时间：
2004-10-01
期刊：
影响因子：
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通讯作者：
Heitman, J
中科院分区：
文献类型：
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作者：
Kraus, PR;Boily, MJ;Heitman, J
在37℃下生存和增殖的能力是病原微生物的重要毒力属性。使用部分基因组微阵列分析人类致病真菌新型隐球菌在 37 摄氏度生长期间的基因表达。具有参与应激反应的直系同源基因在 37°C 的生长过程中被诱导，这表明新型隐球菌使用保守的转录程序在应激条件下改变基因表达。编码转录因子同源物 Mga2 的基因在 37 摄氏度下被诱导，并被发现对高温生长很重要。编码脂肪酸生物合成酶的基因被确定为 Mga2 的潜在靶标，表明膜重塑是适应高生长温度的重要组成部分。 mga2Delta 突变体对麦角甾醇合成抑制剂氟康唑极其敏感，表明膜成分前体的合成具有协调性。出乎意料的是，参与氨基酸和嘧啶生物合成的基因在 37 摄氏度下受到抑制，但发现这些途径的组成部分是高温生长所必需的。我们的研究结果证明了部分基因组微阵列在描绘有助于微生物发病机制的调控级联方面的效用。
The ability to survive and proliferate at 37 degreesC is an essential virulence attribute of pathogenic microorganisms. A partial-genome microarray was used to profile gene expression in the human-pathogenic fungus Cryptococcus neoformans during growth at 37 degreesC. Genes with orthologs involved in stress responses were induced during growth at 37 degreesC, suggesting that a conserved transcriptional program is used by C. neoformans to alter gene expression during stressful conditions. A gene encoding the transcription factor homolog Mga2 was induced at 37 degreesC and found to be important for high-temperature growth. Genes encoding fatty acid biosynthetic enzymes were identified as potential targets of Mga2, suggesting that membrane remodeling is an important component of adaptation to high growth temperatures. mga2Delta mutants were extremely sensitive to the ergosterol synthesis inhibitor fluconazole, indicating a coordination of the synthesis of membrane component precursors. Unexpectedly, genes involved in amino acid and pyrimidine biosynthesis were repressed at 37 degreesC, but components of these pathways were found to be required for high-temperature growth. Our findings demonstrate the utility of even partial-genome microarrays for delineating regulatory cascades that contribute to microbial pathogenesis.