Candida glabrata tryptophan-based pigment production via the Ehrlich pathway
Candida glabrata tryptophan-based pigment production via the Ehrlich pathway
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DOI：
10.1111/j.1365-2958.2010.07052.x
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发表时间：
2010-04-01
影响因子：
3.6
通讯作者：
Hube, Bernhard
中科院分区：
文献类型：
--
作者：
Brunke, Sascha;Seider, Katja;Hube, Bernhard
P>；色素有助于许多真菌的致病性，主要是通过保护真菌细胞免受宿主防御活动的影响。在这里，我们解剖了人类病原菌光滑假丝酵母色氨酸来源的色素的生物合成途径，鉴定了参与色素产生的关键基因，并开始阐明该色素可能的生物学功能。利用转录分析和转座子插入文库，我们已经确定了与色素产生相关的基因。定点缺失突变体显示该色素是色氨酸降解的Ehrlich途径的副产物：缺乏色氨酸上调的芳香族氨基转移酶(Aro8)的突变体显着减少了色素沉着，并且该蛋白的重组表达版本足以在体外产生色素。色素的产生受到严格的控制，因为合成受到替代氮源、碳源、环状AMP和氧气的影响。光肩星天牛在色素诱导培养基上生长后，对过氧化氢的抗性增强，这是色素缺陷突变株所未观察到的。此外，有色酵母细胞在暴露于人中性粒细胞时有更高的存活率，并在单层人上皮细胞模型中导致损伤增加，这表明色素可能在与宿主细胞相互作用过程中发挥作用。
P>Pigments contribute to the pathogenicity of many fungi, mainly by protecting fungal cells from host defence activities. Here, we have dissected the biosynthetic pathway of a tryptophan-derived pigment of the human pathogen Candida glabrata, identified key genes involved in pigment production and have begun to elucidate the possible biological function of the pigment. Using transcriptional analyses and a transposon insertion library, we have identified genes associated with pigment production. Targeted deletion mutants revealed that the pigment is a by-product of the Ehrlich pathway of tryptophan degradation: a mutant lacking a tryptophan-upregulated aromatic aminotransferase (Aro8) displayed significantly reduced pigmentation and a recombinantly expressed version of this protein was sufficient for pigment production in vitro. Pigment production is tightly regulated as the synthesis is affected by the presence of alternative nitrogen sources, carbon sources, cyclic AMP and oxygen. Growth of C. glabrata on pigment inducing medium leads to an increased resistance to hydrogen peroxide, an effect which was not observed with a mutant defective in pigmentation. Furthermore, pigmented yeast cells had a higher survival rate when exposed to human neutrophils and caused increased damage in a monolayer model of human epithelia, indicating a possible role of pigmentation during interactions with host cells.