Chybowska Aleksandra D, Helmstetter Nicolas, Rajendram Dunstan, Bibby David, Borman Andrew M, Farrer Rhys A
Institute of Genetics and Cancer, University of Edinburgh, Western General Hospital, Edinburgh, UK.
Medical Research Council, Centre for Medical Mycology, University of Exeter, Exeter, UK.
Methods Mol Biol. 2025;2955:247-262. doi: 10.1007/978-1-0716-4702-8_12.
Mycetoma is a neglected tropical disease, characterized by slowly evolving tumorous subcutaneous masses containing either bacteria (e.g., Actinomycetoma) or fungi (e.g., Eumycetoma; Madura foot). The fungal agents of mycetoma, including several genera belonging to the Pleosporales order of Ascomycetes, were designated high-priority pathogens in the WHO Fungal Priority Pathogens List of 2023 to signal the need for additional research and development and public health action. Despite this, many of the fungal causative agents are poorly described, especially in terms of the genomic basis for disease, their epidemiology, and evolutionary history. Recently, the new genus Emarellia was described, including two sister species, E. grisea and E. paragrisea. To gain insights into the virulence and/or pathogenicity features of eumycetoma, we describe the first genome assembly and gene annotation for Emarellia grisea and compare this genome assembly to those currently available for other agents of eumycetoma and close relatives, Madurella mycetomatis and Trematosphaeria pertusa. We also describe the gene annotation for the genome assembly of Nigrograna (formerly Biatriospora) mackinnonii, which hitherto lacked annotation. Our genome assembly comprises 691 contigs representing 28.23 Mb of sequence, with very low repeat content. Genes uniquely encoded by E. grisea included an enrichment of secretion signals, suggesting possible new virulence factors. We also found that E. grisea produces a diverse array of endo- and exopeptidases, which may contribute to its virulence and drug resistance. We anticipate that our genomic resource and analysis will benefit future studies on the genomic basis for pathogenicity in neglected fungal agents causing eumycetoma or similar subcutaneous lesions in humans.
足菌肿是一种被忽视的热带疾病,其特征是皮下出现缓慢发展的肿瘤样肿块,肿块中含有细菌(如放线菌性足菌肿)或真菌(如真菌性足菌肿;马杜拉足)。足菌肿的真菌病原体,包括属于子囊菌纲格孢腔菌目的几个属,在《2023年世界卫生组织真菌重点病原体清单》中被列为高度优先病原体,这表明需要进一步的研究、开发以及公共卫生行动。尽管如此,许多真菌病原体的描述仍很欠缺,尤其是在疾病的基因组基础、流行病学和进化史方面。最近,新属埃马雷利菌属被描述,包括两个姊妹种,即灰色埃马雷利菌和近灰色埃马雷利菌。为了深入了解真菌性足菌肿的毒力和/或致病性特征,我们描述了灰色埃马雷利菌的首个基因组组装和基因注释,并将该基因组组装与目前可获得的其他真菌性足菌肿病原体以及近亲马杜拉分支菌和穿孔 Trematosphaeria 的基因组组装进行比较。我们还描述了迄今缺乏注释的马氏黑粒菌(原双孢霉属)基因组组装的基因注释。我们的基因组组装由691个重叠群组成,代表28.23 Mb的序列,重复含量非常低。灰色埃马雷利菌独特编码的基因包括丰富的分泌信号,表明可能存在新的毒力因子。我们还发现灰色埃马雷利菌产生多种内切和外切肽酶,这可能有助于其毒力和耐药性。我们预计,我们的基因组资源和分析将有利于未来对导致人类真菌性足菌肿或类似皮下病变的被忽视真菌病原体致病性的基因组基础的研究。