Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
mBio. 2012 Sep 4;3(5):e00259-12. doi: 10.1128/mBio.00259-12. Print 2012.
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.
导致脚气的主要原因是红色毛癣菌，一种寄生在人类皮肤的真菌。为了便于对这些真菌进行分子分析，我们对红色毛癣菌以及四个相关物种（须毛癣菌、絮状表皮癣菌、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存在差异。这些真菌的基因组高度同源，但含有其他与人类相关的真菌中没有发现的基因家族扩张。表皮癣菌基因组富含含有 LysM 结构域的基因家族，该结构域可以结合几丁质和潜在相关的碳水化合物。这些 LysM 结构域在肽的与底物结合有关的区域与其他物种的 LysM 结构域在序列上存在差异。表皮癣菌还编码了一系列具有未知特异性的新型真菌特异性激酶，包括无功能的拟激酶，它们可能通过与底物中的激酶位点竞争来抑制磷酸化，从而作为别构效应物或作为信号转导的支架发挥作用。表皮癣菌还富含大量合成次级代谢产物的酶，包括表皮癣菌特有的基因，这些基因可能合成新的化合物。最后，表皮癣菌富含几类对在角蛋白组织上生长和获取营养物质至关重要的蛋白酶。尽管交配能力存在差异，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理解表皮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应对宿主免疫反应至关重要的基因家族。
