Department of Molecular Biology & Biotechnology, University of Kalyani, West Bengal 741235, India.
Department of Bioscience & Biotechnology, Banasthali Vidyapith, Rajasthan 304022, India.
Gene. 2021 May 15;780:145530. doi: 10.1016/j.gene.2021.145530. Epub 2021 Feb 23.
Candida spp. have attracted considerable attention as they cause serious human diseases in immunocompromised individuals. The genomes of the pathogenic Candida spp. have been sequenced, but systemic characterizations of their kinomes are yet to be reported. As in various eukaryotes, the protein kinases play crucial regulatory roles in pathogenicity of Candida. Increased frequency of antifungal resistance in Candida spp. requires significant attention to explore novel therapeutic molecules for their control. The present in-silico study involves novel bioinformatics strategies to identify the kinase proteins and their potential drug targets with the purpose to combat fungal infections. The study reports 103, 107 and 106 kinase proteins from 3 Candida spp., C. albicans, C. parapsilosis and C. tropicalis, respectively. Moreover, 79 common kinase proteins were identified, of which 54 proteins play essential roles in Candida spp. and 42 proteins were human non-homologues. Among the essential and human non-homologous protein kinases, 9 were found to be common essential human non-homologues, of which 6 are uniquely present in Candida. These 6 protein kinases namely, Hsl1, Npr1, Ptk2, Kin2, Ksp1 and orf19.3854 (CAALFM_CR06040WA) are involved in various molecular and cellular processes regulating virulence or pathogenicity. Further, these 6 kinases are prioritized as potential drug targets and explored for discovering new lead compounds against candidiasis. The drug repurposing approach for these 6 kinases show 13 approved drugs and investigational compounds that might play substantial inhibitory roles during combating candidiasis.
念珠菌属已引起人们的广泛关注，因为它们会导致免疫功能低下个体的严重人类疾病。致病性念珠菌属的基因组已经测序，但它们的激酶组的系统特征尚未报道。与各种真核生物一样，蛋白激酶在念珠菌属的致病性中发挥着至关重要的调节作用。念珠菌属中抗真菌药物耐药性的频率增加，需要引起高度重视，以探索控制该疾病的新治疗分子。本研究采用新的生物信息学策略，识别激酶蛋白及其潜在的药物靶点，以对抗真菌感染。该研究分别从 3 种念珠菌属（白色念珠菌、近平滑念珠菌和热带念珠菌）中报告了 103、107 和 106 种激酶蛋白。此外，还鉴定出 79 种共同的激酶蛋白，其中 54 种蛋白在念珠菌属中发挥重要作用，42 种蛋白为人源非同源蛋白。在必需和人源非同源蛋白激酶中，有 9 种被鉴定为人源共同必需非同源蛋白激酶，其中 6 种蛋白仅存在于念珠菌属中。这 6 种蛋白激酶（Hsl1、Npr1、Ptk2、Kin2、Ksp1 和 orf19.3854（CAALFM_CR06040WA））参与调节毒力或致病性的各种分子和细胞过程。此外，这 6 种激酶被优先作为潜在的药物靶点，并用于发现抗念珠菌病的新先导化合物。这 6 种激酶的药物再利用方法显示出 13 种已批准的药物和研究性化合物，这些药物可能在对抗念珠菌病方面发挥重要的抑制作用。
