Novel Pathogenic Mucorales Identified Using the Silkworm Infection Model

Suresh Panthee,Atmika Paudel,Hiroshi Hamamoto,Kazuhisa Sekimizu,Yayoi Nishiyama

doi:10.3390/jof7110995

Suresh Panthee, Atmika Paudel + Show 3 more

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https://doi.org/10.3390/jof7110995

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Abstract

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 (Bombyx mori) 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 Mucor orantomantidis, and strain 827-14 claded with Backusella lamprospora. All the strains had a cold-sensitive phenotype with their inability to grow prominently at 4 °C. Mucor 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 Mucor 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.

Highlights

Fungi help maintain the diversity of the ecosystem and are critical to nutrient-cycling by degrading dead organic materials [1]
This result was consistent with the constructed phylogenetic tree using MEGA X [19], where we found that strains 1-3, 5-3, and S286-1101 were claded with M. orantomantidis, and strain 827-14 was claded with B. lamprospora (Figure 1)
20These h, indicating ability the of these fungi to rapidly kill silkworms. These results indicated the pathogenicity of spores of newly(Supplementary identified fungi against silkworms

Summary

Introduction

Fungi help maintain the diversity of the ecosystem and are critical to nutrient-cycling by degrading dead organic materials [1]. Fungi with agricultural, ecological, economic, biotechnological, and medical importance have been identified. Invasive fungal diseases account for a majority of complications among immunocompromised patients worldwide [2]. Fungi of the order Mucorales cause mucormycosis, a rare but highly fatal fungal infection. They can cause cutaneous, rhino-orbital, pulmonary, rhino-cerebral, and disseminated bloodstream infections; the severity and prognosis largely depend upon the infection type. The fatality rate is very high [3] with 96% among patients with disseminated infections [4]. The incidence of mucormycosis is rapidly increasing, especially in developing countries like India and Nepal, where Mucorales were mostly found to cause rhino-orbito-cerebral infections

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Conclusion