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Measurements of Physiological Stress Responses in C. Elegans
Published on: May 21, 2020
Hog1-mediated stress tolerance in the pathogenic fungus Trichosporon asahii
Yasuhiko Matsumoto1, Yu Sugiyama2, Tae Nagamachi2
1Department of Microbiology, Meiji Pharmaceutical University, 2-522-1, Noshio, Kiyose, Tokyo, 204-8588, Japan. ymatsumoto@my-pharm.ac.jp.
Abstract:
Trichosporon asahii is an opportunistic pathogenic fungus that causes severe and sometimes fatal infections in immunocompromised patients. Hog1, a mitogen-activated protein kinase, regulates the stress resistance of some pathogenic fungi, however its role in T. asahii has not been investigated. Here, we demonstrated that the hog1 gene-deficient T. asahii mutant is sensitive to high temperature, cell membrane stress, oxidative stress, and antifungal drugs. Growth of the hog1 gene-deficient T. asahii mutant was delayed at 40 °C. The hog1 gene-deficient T. asahii mutant also exhibited sensitivity to sodium dodecyl sulfate, hydrogen peroxide, menadione, methyl methanesulfonate, UV exposure, and antifungal drugs such as amphotericin B under a glucose-rich condition. Under a glucose-restricted condition, the hog1 gene-deficient mutant exhibited sensitivity to NaCl and KCl. The virulence of the hog1 gene-deficient mutant against silkworms was attenuated. Moreover, the viability of the hog1 gene-deficient mutant decreased in the silkworm hemolymph. These phenotypes were restored by re-introducing the hog1 gene into the gene-deficient mutant. Our findings suggest that Hog1 plays a critical role in regulating cellular stress responses in T. asahii.
Insights
The Hog1 protein is crucial for the survival of Trichosporon asahii, a fungus causing infections in immunocompromised individuals. Its absence increases susceptibility to various stresses and reduces fungal virulence.
Area of Science:
- Mycology
- Molecular Biology
- Infectious Diseases
Background:
- Trichosporon asahii is an opportunistic pathogen causing severe infections in immunocompromised patients.
- The mitogen-activated protein kinase Hog1 is known to regulate stress resistance in other pathogenic fungi, but its role in T. asahii remains uncharacterized.
Purpose of the Study:
- To investigate the function of the Hog1 protein in Trichosporon asahii.
- To determine the role of Hog1 in T. asahii's response to environmental stresses and its virulence.
Main Methods:
- Gene deletion of hog1 in T. asahii to create a mutant.
- Phenotypic analysis of the hog1-deficient mutant under various stress conditions (high temperature, oxidative, osmotic, drug sensitivity).
- Assessment of fungal virulence using a silkworm infection model.
Main Results:
- The hog1 gene-deficient T. asahii mutant showed increased sensitivity to high temperature (40°C), cell membrane stress (SDS), oxidative stress (H2O2, menadione), genotoxic stress (MMS, UV), and antifungal drugs (amphotericin B).
- The mutant exhibited osmotic sensitivity (NaCl, KCl) under glucose-restricted conditions.
- Virulence in silkworms was significantly attenuated, with reduced viability in hemolymph, and these defects were complemented by reintroducing the hog1 gene.
Conclusions:
- Hog1 is essential for T. asahii's cellular stress response, including resistance to heat, oxidative damage, and antifungal agents.
- The Hog1 pathway is critical for T. asahii's virulence and survival within the host.
- Targeting Hog1 could be a potential strategy for treating T. asahii infections.
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