Panthee Suresh, Hamamoto Hiroshi, Nishiyama Yayoi, Paudel Atmika, Sekimizu Kazuhisa
Drug Discoveries by Silkworm Models, Faculty of Pharma-Science, Teikyo University, Hachioji, Tokyo 192-0395, Japan.
Institute of Medical Mycology, Teikyo University, Hachioji, Tokyo 192-0395, Japan.
J Fungi (Basel). 2021 Nov 22;7(11):995. doi: 10.3390/jof7110995.
Mucormycosis, a rare but highly fatal infection, is caused by fungi of the order Mucorales. Due to their ubiquitous nature, reduced susceptibility to antifungals, acid tolerance, and ability to infect immunocompromised patients through rapid dissemination, these fungi have been frequently reported to infect the COVID-19 patients. In order to develop strategies to overcome mucormycosis, it is essential to understand and identify novel Mucorales present in the environment. In this study, we report the identification of four novel pathogenic Mucorales using the silkworm () model. The strains' phylogeny was analyzed using the genome sequence of the large subunit ribosomal ribonucleic acid (LSU rRNA) and the internal transcribed spacer (ITS) region, where strains 1-3, 5-3, and S286-1101 claded with , and strain 827-14 claded with . All the strains had a cold-sensitive phenotype with their inability to grow prominently at 4 °C. sp. 1-3 and 5-3 were characterized by their filamentous and yeast-like growth under aerobic and anaerobic conditions, respectively. The yeast colonies of sp. 5-3 had multipolar budding cells often observed with cleaved cell surfaces under a scanning electron microscope. We further found that these strains were able to kill immunocompromised mice suggesting their pathogenicity to mammals. Our study established an invertebrate model-based screening system to identify novel pathogenic Mucorales from the natural environment and provided a clue towards the rapid increase in COVID-19 related mucormycosis.
毛霉病是一种罕见但致死率很高的感染性疾病，由毛霉目真菌引起。由于这些真菌具有广泛存在的特性、对抗真菌药物敏感性降低、耐酸性以及能够通过快速传播感染免疫功能低下的患者，因此经常有报道称这些真菌会感染新冠肺炎患者。为了制定克服毛霉病的策略，了解和鉴定环境中存在的新型毛霉目真菌至关重要。在本研究中，我们报告了利用家蚕（）模型鉴定出四种新型致病性毛霉目真菌。使用大亚基核糖体核糖核酸（LSU rRNA）和内转录间隔区（ITS）区域的基因组序列对菌株的系统发育进行了分析，其中菌株1-3、5-3和S286-1101与分支在一起，而菌株827-14与分支在一起。所有菌株都具有冷敏感表型，在4℃时无法显著生长。sp. 1-3和5-3的特征分别是在有氧和厌氧条件下呈丝状生长和酵母样生长。sp. 5-3的酵母菌落具有多极芽殖细胞，在扫描电子显微镜下经常观察到细胞表面有裂解现象。我们进一步发现这些菌株能够杀死免疫功能低下的小鼠，表明它们对哺乳动物具有致病性。我们的研究建立了一种基于无脊椎动物模型的筛选系统，用于从自然环境中鉴定新型致病性毛霉目真菌，并为新冠肺炎相关毛霉病的快速增加提供了线索。
