The expression of fungal CotH, human glucose-regulated protein 78 (GRP78), and predicted miRNAs in macrophages and diabetic mice infected with Rhizopus oryzae

Author: mycolabadmin
6/9/2025
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Summary

Mucormycosis is a serious fungal infection caused by Rhizopus oryzae that is particularly dangerous for people with diabetes. This study shows that a fungal protein called CotH3 attaches to a human cell receptor called GRP78, allowing the fungus to invade cells more easily in diabetic patients. The research found that diabetes increases GRP78 production, making fungal invasion more likely, while antifungal treatment (liposomal amphotericin B) can reduce the expression of both CotH3 and GRP78.

Background

Mucormycosis is a life-threatening fungal infection caused by Mucorales species, with Rhizopus oryzae being the most common causative agent. The spore coat protein homolog (CotH) mediates fungal invasion through interaction with glucose-regulated protein 78 (GRP78) receptor on endothelial cells. Diabetes significantly increases susceptibility to mucormycosis due to elevated glucose, iron, and ketone body levels.

Objective

This study examined the gene expressions of spore coat protein homolog 3 (CotH3) and GRP78, along with their target miRNAs, in infected human macrophages, diabetic mice models, and mucormycosis patients. The research aimed to understand the molecular mechanisms of pathogen-host interactions and the role of diabetes in facilitating fungal invasion.

Results

CotH3 and GRP78 gene expressions were significantly upregulated in infected MDMs, with expression increasing over time (6-16 hours). In non-infected diabetic mice, GRP78 expression was elevated, but declined in infected diabetic mice. MiRNA expressions (hsa-miR-16–5p, hsa-miR-93–3p, hsa-miR-335–5p) were downregulated in infected macrophages. In clinical samples, GRP78 expression was 117-fold higher in untreated patients but decreased 87-fold after treatment.

Conclusion

Diabetes amplifies GRP78 expression, increasing vulnerability to mucormycosis. The increased CotH3 and GRP78 gene expressions in infected macrophages reflect pathogen-host interactions, while reduced miRNA levels indicate sustained fungal survival. These findings suggest that CotH3, GRP78, and miRNAs could serve as biomarkers for early detection and monitoring of mucormycosis treatment efficacy.

Published in:Microbiology Spectrum,
Study Type:Experimental Study,
Source: 10.1128/spectrum.02852-24, PMID: 40488471