Investigating Common Pathogenic Mechanisms between <i>Homo sapiens</i> and Different Strains of <i>Candida albicans</i> for Drug Design: Systems Biology Approach via Two-Sided NGS Data Identification
<i>Candida albicans</i> (<i>C. albicans</i>) 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...
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doaj-bd0fd2b3db4e4cc7b8413ecff4b5192f2020-11-24T22:09:56ZengMDPI AGToxins2072-66512019-02-0111211910.3390/toxins11020119toxins11020119Investigating Common Pathogenic Mechanisms between <i>Homo sapiens</i> and Different Strains of <i>Candida albicans</i> for Drug Design: Systems Biology Approach via Two-Sided NGS Data IdentificationShan-Ju Yeh0Chun-Chieh Yeh1Chung-Yu Lan2Bor-Sen Chen3Laboratory of Control and Systems Biology, Department of Electrical Engineering, National Tsing Hua University, Hsinchu 30013, TaiwanLaboratory of Control and Systems Biology, Department of Electrical Engineering, National Tsing Hua University, Hsinchu 30013, TaiwanInstitute of Molecular and Cellular Biology, National Tsing Hua University, Hsinchu 30013, TaiwanLaboratory of Control and Systems Biology, Department of Electrical Engineering, National Tsing Hua University, Hsinchu 30013, Taiwan<i>Candida albicans</i> (<i>C. albicans</i>) 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 <i>C. albicans</i>. The aim of this study is to identify drug targets and design a multiple-molecule drug to prevent the infection from <i>C. albicans</i>. To investigate the common and specific pathogenic mechanisms in human oral epithelial OKF6/TERT-2 cells during the <i>C. albicans</i> 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 <i>C. albicans</i>, 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 <i>C. albicans</i>.https://www.mdpi.com/2072-6651/11/2/119<i>C. albicans</i>host–pathogen genetic and epigenetic networkpathogenic mechanismnetwork markermultiple-molecule drug |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Shan-Ju Yeh Chun-Chieh Yeh Chung-Yu Lan Bor-Sen Chen |
spellingShingle |
Shan-Ju Yeh Chun-Chieh Yeh Chung-Yu Lan Bor-Sen Chen Investigating Common Pathogenic Mechanisms between <i>Homo sapiens</i> and Different Strains of <i>Candida albicans</i> for Drug Design: Systems Biology Approach via Two-Sided NGS Data Identification Toxins <i>C. albicans</i> host–pathogen genetic and epigenetic network pathogenic mechanism network marker multiple-molecule drug |
author_facet |
Shan-Ju Yeh Chun-Chieh Yeh Chung-Yu Lan Bor-Sen Chen |
author_sort |
Shan-Ju Yeh |
title |
Investigating Common Pathogenic Mechanisms between <i>Homo sapiens</i> and Different Strains of <i>Candida albicans</i> for Drug Design: Systems Biology Approach via Two-Sided NGS Data Identification |
title_short |
Investigating Common Pathogenic Mechanisms between <i>Homo sapiens</i> and Different Strains of <i>Candida albicans</i> for Drug Design: Systems Biology Approach via Two-Sided NGS Data Identification |
title_full |
Investigating Common Pathogenic Mechanisms between <i>Homo sapiens</i> and Different Strains of <i>Candida albicans</i> for Drug Design: Systems Biology Approach via Two-Sided NGS Data Identification |
title_fullStr |
Investigating Common Pathogenic Mechanisms between <i>Homo sapiens</i> and Different Strains of <i>Candida albicans</i> for Drug Design: Systems Biology Approach via Two-Sided NGS Data Identification |
title_full_unstemmed |
Investigating Common Pathogenic Mechanisms between <i>Homo sapiens</i> and Different Strains of <i>Candida albicans</i> for Drug Design: Systems Biology Approach via Two-Sided NGS Data Identification |
title_sort |
investigating common pathogenic mechanisms between <i>homo sapiens</i> and different strains of <i>candida albicans</i> for drug design: systems biology approach via two-sided ngs data identification |
publisher |
MDPI AG |
series |
Toxins |
issn |
2072-6651 |
publishDate |
2019-02-01 |
description |
<i>Candida albicans</i> (<i>C. albicans</i>) 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 <i>C. albicans</i>. The aim of this study is to identify drug targets and design a multiple-molecule drug to prevent the infection from <i>C. albicans</i>. To investigate the common and specific pathogenic mechanisms in human oral epithelial OKF6/TERT-2 cells during the <i>C. albicans</i> 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 <i>C. albicans</i>, 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 <i>C. albicans</i>. |
topic |
<i>C. albicans</i> host–pathogen genetic and epigenetic network pathogenic mechanism network marker multiple-molecule drug |
url |
https://www.mdpi.com/2072-6651/11/2/119 |
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