RNA-seq Total tag counts per sequence library.

Eumycetoma is a neglected tropical subcutaneous disease most commonly caused by the fungus Madurella mycetomatis. Currently, eumycetoma is treated by a combination of antifungal therapy and surgery, with limited success rates. To identify novel drug targets we used an in silico approach to determine the kinases present in M. mycetomatis genome and rank them as potential drug targets. In total 132 predicted kinases were identified in M. mycetomatis, of which 21 were predicted to be essential for fungal viability and 4 of these had no human orthologues. Two were linked to the Cell Wall Integrity (CWI) signalling pathway and were expressed in a Galleria mellonella infection model. Several kinase inhibitors were identified after in silico modelling, however only 8 were able to inhibit growth. Five had predicted binding affinity with components of the CWI. Altogether, the CWI shows potential as a drug target for further evaluation.真菌性足菌肿（Eumycetoma）是一种被忽视的热带皮下感染性疾病，其最常见的致病真菌为马杜拉霉（Madurella mycetomatis）。目前，真菌性足菌肿采用抗真菌治疗联合外科手术的方案进行治疗，但临床成功率有限。为鉴定新型药物靶点，本研究采用计算机模拟（in silico）分析方法，对马杜拉霉基因组中的激酶进行预测，并将其列为潜在药物靶点进行优先级排序。研究共在马杜拉霉基因组中鉴定出132个预测激酶，其中21个被预测为维持真菌存活所必需的激酶，且这21个激酶中有4个未发现人类直系同源物。另有2个激酶与细胞壁完整性（Cell Wall Integrity, CWI）信号通路相关，且在大蜡螟（Galleria mellonella）感染模型中呈表达状态。通过计算机模拟建模筛选，共鉴定出多种激酶抑制剂，但仅8种可有效抑制真菌生长，其中5种可与CWI通路组分产生预测结合亲和力。综上，CWI信号通路具备作为进一步评估的药物靶点的潜力。