Decoding the host-pathogen interspecies molecular crosstalk during oral candidiasis in humans: an in silico analysis

Introduction: The objective of this study is to investigate the interaction between Candida albicans and human proteins during oral candidiasis, with the aim of identifying pathways through which the pathogen subverts host cells. Methods: A comprehensive list of interactions between human proteins and C. albicans was obtained from the Human Protein Interaction Database using specific screening criteria. Then, the genes that exhibit differential expression during oral candidiasis in C. albicans were mapped with the list of human-Candida interactions to identify the corresponding host proteins. The identified host proteins were further compared with proteins specific to the tongue, resulting in a final list of 99 host proteins implicated in oral candidiasis. The interactions between host proteins and C. albicans proteins were analyzed using the STRING database, enabling the construction of protein-protein interaction networks. Similarly, the gene regulatory network of Candida proteins was reconstructed using data from the PathoYeastract and STRING databases. Core module proteins within the targeted host protein-protein interaction network were identified using ModuLand, a Cytoscape plugin. The expression levels of the core module proteins under diseased conditions were assessed using data from the GSE169278 dataset. To gain insights into the functional characteristics of both host and pathogen proteins, ontology analysis was conducted using Enrichr and YeastEnrichr, respectively. Result: The analysis revealed that three Candida proteins, HHT21, CYP5, and KAR2, interact with three core host proteins, namely, ING4 (in the DNMT1 module), SGTA, and TOR1A. These interactions potentially impair the immediate immune response of the host against the pathogen. Additionally, differential expression analysis of fungal proteins and their transcription factors in Candida-infected oral cell lines indicated that Rob1p, Tye7p, and Ume6p could be considered candidate transcription factors involved in instigating the pathogenesis of oral candidiasis during host infection. Conclusion: Our study provides a molecular map of the host-pathogen interaction during oral candidiasis, along with potential targets for designing regimens to overcome oral candidiasis, particularly in immunocompromised individuals.