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Published on: June 6, 2025
The influence of the mating type on virulence of Mucor irregularis
Wenqi Xu1, Guanzhao Liang1, Jingwen Peng1
1Department of Mycology, Institute of Dermatology, Chinese Academy of Medical, Sciences and Peking Union Medical College, No. 12 Jiang Wangmiao Street, Nanjing, 210042, Jiangsu, People's Republic of China.
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.
Insights
Mucor irregularis mating types influence cutaneous infection severity. The (+) mating type showed enhanced virulence in a mouse model, despite most clinical isolates being (-).
Area of Science:
- Medical Mycology
- Fungal Pathogenesis
- Molecular Mycology
Background:
- Mucor irregularis is an emerging fungal pathogen causing cutaneous infections with potential for severe outcomes.
- The mechanisms underlying M. irregularis pathogenesis remain largely uncharacterized.
- Fungal mating types can influence virulence, a phenomenon observed in other Mucorales.
Purpose of the Study:
- To characterize the mating type locus of M. irregularis.
- To determine the mating type ratio among clinical isolates.
- To investigate the role of mating types in M. irregularis pathogenesis and disease severity.
Main Methods:
- Genomic analysis to identify mating type alleles (SexP and SexM) and confirm heterothallism.
- Infection of a mouse model to assess inflammatory responses and pathological effects of different mating types.
- Analysis of cytokine profiles and immune cell populations (Th-1, Th-2, Th-17) in infected mice.
Main Results:
- Genomic data confirmed M. irregularis is heterothallic with two mating types: (+) bearing SexP and (-) bearing SexM alleles.
- Mice infected with the (+) mating type exhibited enhanced disease severity and progression, with altered inflammatory responses and cytokine profiles.
- A (+/0) mutant strain showed impaired mating but increased virulence compared to the (-) mating type.
- Despite higher observed virulence in the (+) type, most clinical isolates were of the (-) mating type.
Conclusions:
- Mating type genes (MAT genes) are involved in sexual fertility in M. irregularis.
- The mating type significantly influences the severity of cutaneous infections caused by M. irregularis.
- Further research is needed to reconcile the higher virulence of the (+) mating type with the prevalence of the (-) mating type in clinical settings.
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