Investigating Common Pathogenic Mechanisms between Homo sapiens and Different Strains of Candida albicans for Drug Design: Systems Biology Approach via Two-Sided NGS Data Identification

Abstract

Candida albicans (C. albicans) is the most prevalent fungal species. Although it is a healthy microbiota, genetic and epigenetic alterations in host and pathogen, and microenvironment changes would lead to thrush, vaginal yeast infection, and even hematogenously disseminated infection. Despite the fact that cytotoxicity is well-characterized, few studies discuss the genome-wide genetic and epigenetic molecular mechanisms between host and C. albicans. The aim of this study is to identify drug targets and design a multiple-molecule drug to prevent the infection from C. albicans. To investigate the common and specific pathogenic mechanisms in human oral epithelial OKF6/TERT-2 cells during the C. albicans infection in different strains, systems modeling and big databases mining were used to construct candidate host–pathogen genetic and epigenetic interspecies network (GEIN). System identification and system order detection are applied on two-sided next generation sequencing (NGS) data to build real host–pathogen cross-talk GEINs. Core host–pathogen cross-talk networks (HPCNs) are extracted by principal network projection (PNP) method. By comparing with core HPCNs in different strains of C. albicans, common pathogenic mechanisms were investigated and several drug targets were suggested as follows: orf19.5034 (YBP1) with the ability of anti-ROS; orf19.939 (NAM7), orf19.2087 (SAS2), orf19.1093 (FLO8) and orf19.1854 (HHF22) with high correlation to the hyphae growth and pathogen protein interaction; orf19.5585 (SAP5), orf19.5542 (SAP6) and orf19.4519 (SUV3) with the cause of biofilm formation. Eventually, five corresponding compounds—Tunicamycin, Terbinafine, Cerulenin, Tetracycline and Tetrandrine—with three known drugs could be considered as a potential multiple-molecule drug for therapeutic treatment of C. albicans.

Next-Generation Sequencing Applications for the Study of Fungal Pathogens

“…is the most frequent cause of fungal disease in humans. By establishing genetic and epigenetic interspecies networks of different strains of Candida albicans and their hosts through two-sided NGS data identification, Yeh et al [ 38 ] extracted core host–pathogen cross-talk networks. In addition to screening and identifying specific fungal types, NGS can be used to assess AMR.…”

“…Furthermore, the functional channels and pathogenic and defense mechanisms of C. albicans were studied, as were potential drug targets and multiple-molecule drugs for treating C. albicans infections [ 38 ]. By combining NGS with Fourier transform infrared (FTIR) spectroscopy, 256 phenotypes and genotypes of pathogenic Candida strains were identified.…”

Systems Medicine Design based on Systems Biology Approaches and Deep Neural Network for Gastric Cancer

“…Moreover, one study has proposed a mathematical model of the plant clock using biological hypotheses and parameters solved by optimization methods to gain insights into the clock components within core mechanisms [22]. Systems biology approaches have been used to identify essential biomarkers and propose potential drugs based on molecular mechanisms and pathogenic mechanisms in papillary thyroid cancer and two strains of Candida albicans infection [23,24]. Systems biology approaches with modeling techniques enable us to elucidate the pathways, which are critically involved in tumor formation and progression, consequences of altered cell behavior in tissue environment and effects of molecular therapeutics [25].…”

In Vitro Evaluation of Antibacterial and Antifungal Properties of Some New 1, 3, 4-Oxadiazole Derivatives Containing Phenyl Group

“…Different strains of Candida are known to cause infections. Recent epidemiological studies have shown that drug-resistant species of Candida, like C. glabrata, C. krusei, C. tropicalis, and C. parapsilosis, are gradually replaced C. albicans in diseases [12] . Due to the spread of fungal infections and the increase in the use of antifungal drugs such as azoles, a significant increase in the resistance of Candida species to antifungal compounds is expected [13] .…”