Transcriptional profile of the human skin pathogenic fungus Mucor irregularis in response to low oxygen.

ABSTRACT

Mucormycosis is one of the most invasive mycosis and has caused global concern in public health. Cutaneous mucormycosis caused by Mucor irregularis (formerly Rhizomucor variabilis) is an emerging disease in China. To survive in the human body, M. irregularis must overcome the hypoxic (low oxygen) host microenvironment. However, the exact molecular mechanism of its pathogenicity and adaptation to low oxygen stress environment is relatively unexplored. In this study, we used Illumina HiSeq technology (RNA-Seq) to determine and compare the transcriptome profile of M. irregularis CBS103.93 under normal growth condition and hypoxic stress. Our analyses demonstrated a series of genes involved in TCA, glyoxylate cycle, pentose phosphate pathway, and GABA shunt were down-regulated under hypoxic condition, while certain genes in the lipid/fatty acid metabolism and endocytosis were up-regulated, indicating that lipid metabolism was more active under hypoxia. Comparing the data with other important human pathogenic fungi such as Aspergillus spp., we found that the gene expression pattern and metabolism in responses to hypoxia in M. irregularis were unique and different. We proposed that these metabolic changes can represent a species-specific hypoxic adaptation in M. irregularis, and we hypothesized that M. irregularis could use the intra-lipid pool and lipid secreted in the infection region, as an extracellular nutrient source to support its hypoxic growth. Characterizing the significant differential gene expression in this species could be beneficial to uncover their role in hypoxia adaptation and fungalpathogenesis and further facilitate the development of novel targets in disease diagnosis and treatment against mucormycosis.