The influence of the mating type on virulence of Mucor irregularis

Wenqi Xu,Qiong Wang,Guixia Lv,Dongmei Li,Yongnian Shen,Meihua Fu,Guanzhao Liang,Huan Mei,Jingwen Peng,Weida Liu,Zhimin Long,Clement K M Tsui

doi:10.1038/s41598-017-10954-2

Abstract

Mucor irregularis is an emerging fungal pathogen that cause cutaneous infection and could cause death. However, little is known about its mechanism of pathogenesis. There is evidence suggesting virulence vary with mating types in fungi, including the Mucorales. Here, we characterized the mating type locus of M. irregularis and the mating type ratio of 17 clinical isolates in China. Genomic data indicated M. irregularis is heterothallic having two mating types – bearing either SexP or SexM allele. Also, we employed a mice model to study the inflammation and pathological effects of different mating types. The comparison of the inflammatory response, cytokine profiles and Th-1, Th-2 and Th-17 cells numbers in each mating type treated mice showed that the severity and disease progress were enhanced in (+) mating type treated mice. One (+/0) mutant strain, with multiple mutations at the mating locus, had defects in sexual mating ability but appeared to be more virulent than the (−) mating type. Although (+) mating type appeared to be more virulent, most of our clinical isolates presented belonged to (−) mating type. Our findings support the involvement of MAT genes in sexual fertility, and the influence of mating type on the severity of cutaneous infection.

Highlights

Mucormycosis is an invasive fungal infection that almost invariably occurs in immunocompromised patients and it is the third most common life-threatening fungal infection following aspergillosis and candidiasis[1]
These studies revealed that the mating system in Mucorales were regulated by divergent alleles of a single gene - SexM/SexP, which consist of a high mobility group (HMG) transcription factor gene flanked by genes encoding a triose phosphate transporter homolog (TPT) and an RNA helicase[21,22,23]
We found the growth rates and the optimal growth temperatures of clinical isolates were similar to the standard strain on malt extract agar (MEA) at room temperature (~21 °C), 24 °C, 28 °C, 32 °C, 35 °C, and 38 °C

Summary

Introduction

Mucormycosis is an invasive fungal infection that almost invariably occurs in immunocompromised patients and it is the third most common life-threatening fungal infection following aspergillosis and candidiasis[1]. Sexual reproduction has not been demonstrated in the Mucorales until recently, for example, Rhizopus miehei, Mucor circinelloides, Phycomyces blakesleeanus, Rhizopus oryzae and other human pathogenic members of the Mucorales[18,19,20]. These studies revealed that the mating system in Mucorales were regulated by divergent alleles of a single gene - SexM/SexP, which consist of a high mobility group (HMG) transcription factor gene flanked by genes encoding a triose phosphate transporter homolog (TPT) and an RNA helicase[21,22,23]. The relationship between genetic/ genomic variation and the level of virulence is poorly investigated

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Results

Conclusion