Comparative analysis of plant and animal fungal pathogens to identify putative drug targets- a subtractive genomics approach

The recent proliferation and the availability of the complete sequence information of the pathogenic fungi has made it possible to carry out the in silico subtractive genome analysis for identification of novel putative drug targets. In this present study subtractive genomic approach is employed to identify novel targets in Ascomycete (Aspergillus fumigatus, Aspergillus nidulans, Gibberella zeae, Ashbya gossypii) and Basidiomycete species (Cryptococcus neoformans). These fungal species act as plant and animal pathogens. Our study reveals that 52 common core proteins are found in the 5 fungal pathogens of our interest from whole proteome comparisons. Further homolog identification was performed against plants and animals using BLASTp and tBLASTn. 17 out of 52 proteins gave considerable results. Unlike all the proteins, C6 transcription factor (XP_753029.1) was found to have no homolog (hits) in plants and animals. In the later step cellular localization of those 17 proteins was found using CELLO v.2.5. The results show that among those 17 proteins, 3 were nuclear proteins, 7 were cytoplasmic proteins, 5 were mitochondrial proteins & 2 were membrane proteins. Membrane proteins were considered for further analysis as they represent the largest group (70%) of effective drug targets. It was found that C6 transcription factor (XP_753029.1) was identified as a membrane protein. Homolog identification and cellular localization prediction results render C6 transcription factor (XP_753029.1) as promising putative drug target as it was involved in unique biochemical pathways in all the 5 fungal pathogens considered for the study and not present in animal or plant host. Molecular Modeling & further screening of the functional inhibitors against these novel targets may result in discovery of novel broad spectrum anti fungal therapy.