Systematic screens of a Candida albicans homozygous deletion library decouple morphogenetic switching and pathogenicity.
Systematic screens of a Candida albicans homozygous deletion library decouple morphogenetic switching and pathogenicity.
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白色念珠菌是人类严重真菌疾病的最常见原因。这种二倍体生物体的等基因无效突变体的产生，需要连续的基因靶向，允许解剖毒力机制。已发表的对这类突变体的分析表明，C。白念珠菌的致病性和在体外经历酵母到菌丝形态转换的能力。然而，大多数研究使用的突变体构建的标记本身是一个毒力决定因素，因此复杂的解释。使用替代标记，我们创建了约3000个纯合缺失菌株，影响674个基因或约11%的C。白色念珠菌基因组。在小鼠模型中筛选感染性和体外形态转换和细胞增殖，我们确定了115个感染性减弱的突变体，其中近一半表现出正常的形态转换和增殖。对这些突变体的分析确定了糖脂，葡萄糖神经酰胺，作为这种病原体合成的第一个小分子，是毒力所必需的。
Candida albicans is the most common cause of serious fungal disease in humans. Creation of isogenic null mutants of this diploid organism, which requires sequential gene targeting, allows dissection of virulence mechanisms. Published analyses of such mutants show a near-perfect correlation between C. albicans pathogenicity and the ability to undergo a yeast-to-hypha morphological switch in vitro. However, most studies used mutants constructed with a marker that is itself a virulence determinant and therefore complicates their interpretation. Using alternative markers, we created ~3000 homozygous deletion strains affecting 674 genes or roughly 11% of the C. albicans genome. Screening for infectivity in a mouse model and for morphological switching and cell proliferation in vitro, we identified 115 infectivity-attenuated mutants, of which nearly half demonstrated normal morphological switching and proliferation. Analysis of such mutants identified the glycolipid, glucosylceramide, as the first small molecule synthesized by this pathogen to be required specifically for virulence.
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影响因子：
3.1
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