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Putative Drug Target Identification in Tinea Causing Pathogen Trichophyton rubrum Using Subtractive Proteomics
Mohamed Hussain Syed Abuthakir1, Thomas Jebastin2, Velusamy Sharmila1
1Biochematics Laboratory, Department of Bioinformatics, Bharathiar University, Coimbatore, Tamil Nadu, 641 046, India.
Abstract:
Trichophyton, important among the three keratinophylic fungi grouped as dermatophytes, is known to cause superficial infections in skin, nail and hair of all the living organisms. The side effects produced by the drugs currently administered to counter these infections have necessitated the search for novel targets. The present study focused on finding putative drug targets in Trichophyton rubrum using the subtractive proteomics approach where its whole proteome was analyzed to find proteins non-homologous to humans inclusive of their gut flora and human protein domain but essential to T. rubrum, to identify sub-cellular localization, functional classification of uncharacterized proteins and to analyze the protein network, druggability and pathway of the targets. The study's strength relies on its addition of important steps namely, non-homology of the pathogen domain to human domain, non-homology to gut microbiota and substantiation of the importance of the targets in networking by node deletion to the existing methods in drug discovery for dermatophytoses. The study has resulted in the identification of two novel drug targets from the whole proteome of T. rubrum that are not present in human and human gut microbiota.
Insights
Researchers identified two novel drug targets in Trichophyton rubrum, a fungus causing skin infections. This study focused on finding targets unique to the fungus, avoiding human or gut bacteria proteins, to develop safer antifungal drugs.
Area of Science:
- Mycology
- Proteomics
- Drug Discovery
Background:
- Dermatophytes, such as Trichophyton, cause superficial fungal infections in skin, nails, and hair.
- Current antifungal drugs have side effects, driving the need for novel therapeutic targets.
- Trichophyton rubrum is a significant dermatophyte responsible for common human infections.
Purpose of the Study:
- To identify novel drug targets in Trichophyton rubrum using subtractive proteomics.
- To find proteins essential for T. rubrum but absent in humans and their gut microbiota.
- To analyze the druggability and pathways of potential drug targets.
Main Methods:
- Subtractive proteomics approach analyzing the whole proteome of T. rubrum.
- Identification of proteins non-homologous to human proteins and human gut flora.
- Analysis of sub-cellular localization, functional classification, protein networks, and druggability.
- Inclusion of pathogen domain non-homology to human domains and gut microbiota.
Main Results:
- Identification of two novel drug targets specific to T. rubrum.
- These targets are absent in both human proteomes and human gut microbiota.
- Analysis confirmed the essentiality and druggability of the identified targets.
Conclusions:
- The study successfully identified two unique drug targets for T. rubrum.
- These targets represent promising candidates for developing safer and more effective antifungal therapies.
- The subtractive proteomics approach, with added validation steps, is effective for dermatophyte drug discovery.
