Department of Microbial Pathogenicity Mechanisms, Hans-Knoell-Institute, Jena, Germany.
Mol Microbiol. 2010 Apr;76(1):25-47. doi: 10.1111/j.1365-2958.2010.07052.x. Epub 2010 Feb 24.
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.
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，我们剖析了人类病原体光滑念珠菌中色氨酸衍生色素的生物合成途径，鉴定了参与色素生成的关键基因，并开始阐明色素的可能生物学功能。我们使用转录分析和转座子插入文库，鉴定了与色素生成相关的基因。靶基因缺失突变体显示，该色素是色氨酸降解的 Ehrlich 途径的副产物：缺乏色氨酸上调芳香族氨基转移酶（Aro8）的突变体显示出明显减少的色素沉着，并且该蛋白的重组表达形式足以在体外产生色素。色素的合成受到替代氮源、碳源、cAMP 和氧气的存在的影响，因此其合成受到严格调控。在诱导色素产生的培养基中生长会导致光滑念珠菌对过氧化氢的抗性增加，而在色素缺陷型突变体中则没有观察到这种现象。此外，当暴露于人中性粒细胞时，着色酵母细胞的存活率更高，并且在人上皮细胞单层模型中引起更大的损伤，表明在与宿主细胞相互作用过程中色素沉着可能具有一定的作用。
