Abstract
Candida albicans causes two types of major infections in humans: superficial infections, such as skin and mucosal infection, and life-threatening systemic infections, like airway and catheter-related blood stream infections. It is a polymorphic fungus with two distinct forms (yeast and hyphal) and the morphological plasticity is strongly associated with many disease causing proteins. In this study, 137 hyphae associated proteins from Candida albicans (C. albicans) were collected from different sources to create a Protein-Protein Interaction (PPI) network. Out of these, we identified 18 hub proteins (Hog1, Hsp90, Cyr1, Cdc28, Pkc1, Cla4, Cdc42, Tpk1, Act1, Pbs2, Bem1, Tpk2, Ras1, Cdc24, Rim101, Cdc11, Cdc10 and Cln3) that were the most important ones in hyphae development. Ontology and functional enrichment analysis of these proteins could categorize these hyphae associated proteins into groups like signal transduction, kinase activity, biofilm formation, filamentous growth, MAPK signaling etc. Functional annotation analysis of these proteins showed that the protein kinase activity to be essential for hyphae formation in Candida. Additionally, most of the proteins from the network were predicted to be localized on cell surface or periphery, suggesting them as the main protagonists in inducing infections within the host. The complex hyphae formation phenomenon of C. albicans is an attractive target for exploitation to develop new antifungals and anti-virulence strategies to combat C. albicans infections. We further tried to characterize few of the most crucial proteins, especially the kinases by their sequence and structural prospects. Therefore, through this article an attempt to understand the hyphae forming protein network analysis has been made to unravel and elucidate the complex pathogenesis processes with the principal aim of systems biological research involving novel Bioinformatics strategies to combat fungal infections.
Highlights
Candida albicans is a pathogenic fungus belonging to the family Saccharomycetaceae which causes life-threatening infections in humans with mortality rate of 40–60% [1, 2, 3]
Protein-Protein Interaction (PPI) network analysis is a crucial approach towards the understanding of the mechanisms of complex biological reactions and their possible outcomes
We focused on building comprehensive network of proteins to analyze their modes of interactions leading to hyphae formation in C. albicans
Summary
Candida albicans is a pathogenic fungus belonging to the family Saccharomycetaceae which causes life-threatening infections in humans with mortality rate of 40–60% [1, 2, 3]. It is an opportunistic pathogen causing circumscribed infections of the skin, nails, and mucocutaneous membranes in healthy people, whereas, becomes aggressive in immune deficient patients due to malignancy, inherited disease, concurrent infection, or medical intervention [4, 5, 6, 7, 8]. 5–8% amongst them suffer from at least four recurrent VVC in a year [16]
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