Comparative genome analysis of Trichophyton rubrum and related dermatophytes reveals candidate genes involved in infection.
Comparative genome analysis of Trichophyton rubrum and related dermatophytes reveals candidate genes involved in infection.
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毛磷脂和相关皮肤植物的比较基因组分析揭示了参与感染的候选基因。
作者：
Martinez DA;Oliver BG;Gräser Y;Goldberg JM;Li W;Martinez-Rossi NM;Monod M;Shelest E;Barton RC;Birch E;Brakhage AA;Chen Z;Gurr SJ;Heiman D;Heitman J;Kosti I;Rossi A;Saif S;Samalova M;Saunders CW;Shea T;Summerbell RC;Xu J;Young S;Zeng Q;Birren BW;Cuomo CA;White TC
运动员脚的主要原因是红色毛癣菌，一种皮肤真菌或人类皮肤的真菌病原体。为了便于皮肤癣菌的分子分析，我们对红色毛癣菌和四个相关种，断端毛癣菌、马毛癣菌、犬小孢子菌和石膏样小孢子菌进行了测序。这些物种在宿主范围、交配和疾病进展方面不同。皮肤癣菌基因组高度共线性，但包含在其他人类相关真菌中未发现的基因家族扩展。皮肤癣菌基因组富含含有LysM结构域的基因家族，该结构域结合几丁质和潜在相关的碳水化合物。这些LysM结构域在序列上与其他物种中可能影响底物结合的肽区域不同。皮肤真菌还编码一组新型的真菌特异性激酶，其特异性未知，包括非功能性假激酶，它们可能通过竞争底物内的激酶位点、充当变构效应物或充当信号传导的支架来抑制磷酸化。皮肤真菌还富含大量合成次级代谢物的酶，包括可以合成新化合物的皮肤真菌特异性基因。最后，皮肤真菌富含几类蛋白酶，这些蛋白酶是真菌生长和角质化组织上营养获取所必需的。尽管交配能力不同，但参与交配和减数分裂的基因在物种间是保守的，这表明在以前未检测到的物种中可能存在隐性交配。这些基因组分析确定了对我们了解皮肤癣菌如何引起慢性感染、它们如何与上皮细胞相互作用以及它们如何对宿主免疫反应做出反应至关重要的基因家族。足癣、股癣、癣和指甲感染都是常见的真菌感染，都是由皮肤真菌引起的。这份报告提出了红色毛癣菌的基因组序列，最常见的原因，运动员的脚，以及其他四个常见的皮肤癣菌。皮肤癣菌基因组富含四类基因，这四类基因可能有助于这些真菌致病的能力。这些包括（i）分泌以降解皮肤的蛋白酶;（ii）激酶，包括假激酶，其参与适应皮肤所必需的信号传导;（iii）次级代谢物，在真菌和宿主之间的相互作用中充当毒素或信号的化合物;和（iv）一类似乎结合和掩蔽细胞壁组分和碳水化合物的蛋白质（LysM），从而避免宿主对真菌的免疫反应。这些基因组序列为未来了解皮肤真菌如何引起疾病的工作提供了坚实的基础。
The major cause of athlete’s foot is Trichophyton rubrum, a dermatophyte or fungal pathogen of human skin. To facilitate molecular analyses of the dermatophytes, we sequenced T. rubrum and four related species, Trichophyton tonsurans, Trichophyton equinum, Microsporum canis, and Microsporum gypseum. These species differ in host range, mating, and disease progression. The dermatophyte genomes are highly colinear yet contain gene family expansions not found in other human-associated fungi. Dermatophyte genomes are enriched for gene families containing the LysM domain, which binds chitin and potentially related carbohydrates. These LysM domains differ in sequence from those in other species in regions of the peptide that could affect substrate binding. The dermatophytes also encode novel sets of fungus-specific kinases with unknown specificity, including nonfunctional pseudokinases, which may inhibit phosphorylation by competing for kinase sites within substrates, acting as allosteric effectors, or acting as scaffolds for signaling. The dermatophytes are also enriched for a large number of enzymes that synthesize secondary metabolites, including dermatophyte-specific genes that could synthesize novel compounds. Finally, dermatophytes are enriched in several classes of proteases that are necessary for fungal growth and nutrient acquisition on keratinized tissues. Despite differences in mating ability, genes involved in mating and meiosis are conserved across species, suggesting the possibility of cryptic mating in species where it has not been previously detected. These genome analyses identify gene families that are important to our understanding of how dermatophytes cause chronic infections, how they interact with epithelial cells, and how they respond to the host immune response. Athlete’s foot, jock itch, ringworm, and nail infections are common fungal infections, all caused by fungi known as dermatophytes (fungi that infect skin). This report presents the genome sequences of Trichophyton rubrum, the most frequent cause of athlete’s foot, as well as four other common dermatophytes. Dermatophyte genomes are enriched for four gene classes that may contribute to the ability of these fungi to cause disease. These include (i) proteases secreted to degrade skin; (ii) kinases, including pseudokinases, that are involved in signaling necessary for adapting to skin; (iii) secondary metabolites, compounds that act as toxins or signals in the interactions between fungus and host; and (iv) a class of proteins (LysM) that appear to bind and mask cell wall components and carbohydrates, thus avoiding the host’s immune response to the fungi. These genome sequences provide a strong foundation for future work in understanding how dermatophytes cause disease.