Kinome analysis of Madurella mycetomatis identified kinases in the cell wall integrity pathway as novel potential therapeutic drug targets in eumycetoma caused by Madurella mycetomatis
- Author: mycolabadmin
- 9/4/2025
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Summary
Eumycetoma is a serious fungal infection that causes large tumors under the skin and is very difficult to treat. Scientists used computer analysis to find special proteins called kinases in the fungus that might be good targets for new drugs. They discovered that proteins involved in the fungus’s cell wall are promising targets, which could lead to better treatments for this neglected disease.
Background
Eumycetoma is a neglected tropical subcutaneous disease most commonly caused by the fungus Madurella mycetomatis. Current treatment involves a combination of antifungal therapy and surgery with limited success rates. Identifying novel drug targets through bioinformatics approaches could improve therapeutic outcomes.
Objective
To identify M. mycetomatis-specific kinases as potential drug targets by analyzing the fungal kinome, comparing it with human and model fungal kinomes, determining essential kinases, and evaluating their expression during infection.
Results
A total of 132 predicted kinases were identified in M. mycetomatis, with 21 predicted as essential for fungal viability. Four essential kinases lacked human orthologues, with two linked to the Cell Wall Integrity pathway and expressed during infection. Eight kinase inhibitors demonstrated growth inhibition, with five showing predicted binding affinity to CWI pathway components.
Conclusion
The Cell Wall Integrity signaling pathway represents a promising novel drug target for M. mycetomatis. This kinome-based approach successfully identified fungal-specific kinases with potential for further drug development and optimization within the Open Source Mycetoma program.
- Published in:PLoS Neglected Tropical Diseases,
- Study Type:In silico and experimental study,
- Source: 10.1371/journal.pntd.0013482, PMID: 40906790