Abstract
Objective: Yeast commonly causes superficial mycoses similar to the dermatophytes. Superficial mycoses were reported with an estimated incidence of ∼140,000,000 cases/year worldwide and most frequently caused by Malassezia globosa and Malassezia furfur. Treatment available for these conditions is limited and with side effects. Moreover, termination of the treatment may result in the reoccurrence of the disease. The objective of this research was to identify the putative drug targets using computational approaches.Methods: The analysis of genome sequence improves the understanding of diseases which leads to better treatment. Comparison of the genome of the pathogen with the host at the molecular level is suitable for performing the sequence based prediction of protein-protein interaction network, which also forms the basis of drug target identification leading to the discovery of new drugs for the improved treatment.Results: Out of 100 pathways of M. globosa, 95 were common to the host and 5 were unique to the pathogen. Total common and unique targets from common pathways are 1704 and 300, respectively. A unique target from unique pathways and 147 from common pathways were non-homologous targets. From this, 46 targets were screened out as essential and processed in the next phase to identify the clustered targets which resulted with three clusters based on their biological role and subcellular location.Conclusion: In this study, putative drug targets were identified in M. globosa using in silico approaches of subtractive genomics and cluster network which will help in the next level of drug discovery such as lead identification for the novel targets.
Highlights
Fungi are becoming ubiquitous in the environment and fungal infections are increasing at an alarming rate causing significant health problems [1]
In this study, putative drug targets were identified in M. globosa using in silico approaches of subtractive genomics and cluster network which will help in the level of drug discovery such as lead identification for the novel targets
Identification of putative drug targets from annotated metabolic pathways available in KEGG using subtractive genomics/ proteomics has been widely used by several researchers in bacterial pathogens [33,34,35,36,37,38]
Summary
Fungi are becoming ubiquitous in the environment and fungal infections are increasing at an alarming rate causing significant health problems [1]. The growing populations of immune compromised individuals with highly susceptibility to fungal pathogens have become a common cause of morbidity and mortality [2]. Fungal infections can be divided into systemic and superficial mycoses. Systemic or deep mycoses are able to infect internal organs. Superficial mycoses affect external part of the skin and hair, and these infections are the most common fungal diseases which affect approximately 25% of the general population worldwide [3]. Out of 14 recognized species of Malassezia [8], a small genome size, spanning ∼9 Mb, Malassezia globosa is associated with skin diseases [9] such as pityriasis versicolor [10], seborrhoeic dermatitis and dandruff [11]. Treatment involves the use of ketoconazole, selenium sulfide, zinc pyrithione, ciclopirox olamine, climbazole [12] but termination of the treatment often leads to the reoccurrence of the symptoms [13]
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