Putative Drug Target Identification in Tinea Causing Pathogen Trichophyton rubrum Using Subtractive Proteomics Approach
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Putative Drug Target Identification in Tinea Causing Pathogen Trichophyton rubrum Using Subtractive Proteomics Approach Mohamed Hussain Syed Abuthakir1 · Thomas Jebastin2 · Velusamy Sharmila1 · Muthusamy Jeyam1 Received: 1 March 2020 / Accepted: 4 July 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
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.
Introduction Dermatophytosis is a superficial infection caused by dermatophytes that invade the skin and nail through hydrolysis of keratin by producing proteolytic enzyme keratinase and grow on the keratinized tissues [1]. Dermatophytosis is also called “tinea” and “ringworm” because they tend to grow outwards on skin and produce ring like pattern [2]. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00284-020-02114-z) contains supplementary material, which is available to authorized users. * Muthusamy Jeyam [email protected]
Trichophyton rubrum, anthropophylic in nature, whose main host is humans may also affect animals and more number of diseases caused by Trichophyton [3]. Drugs used for treatment at present are Azoles, Allylamines, Polyenes, Echinocandins [4]. The antifungal agents are prone to cause toxicity to humans [5] as fungi are also eukaryotes and this makes target identification a highly challenging task in overcoming the problem of drug interaction to the host and gut microbiota. The significance of the study lies in its successful identification of putative drug targets in T. rubrum and the addition of non-homology of domain analysis and node deletion analysis to the existing protocol.
Mohamed Hussain Syed Abuthakir [email protected]
Materials and Methods
Thomas Jebastin [email protected]
Retrieving Protein Datasets and Identifying Related Sequences
Velusamy Sharmila bioinfosharmi88@gmai
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