Abstract

BackgroundDespite clinical research and development in the last decades, infectious diseases remain a top global problem in public health today, being responsible for millions of morbidities and mortalities each year. Therefore, many studies have sought to investigate host-pathogen interactions from various viewpoints in attempts to understand pathogenic and defensive mechanisms, which could help control pathogenic infections. However, most of these efforts have focused predominately on the host or the pathogen individually rather than on a simultaneous analysis of both interaction partners.ResultsIn this study, with the help of simultaneously quantified time-course Candida albicans-zebrafish interaction transcriptomics and other omics data, a computational framework was developed to construct the interspecies protein-protein interaction (PPI) network for C. albicans-zebrafish interactions based on the inference of ortholog-based PPIs and the dynamic modeling of regulatory responses. The identified C. albicans-zebrafish interspecies PPI network highlights the association between C. albicans pathogenesis and the zebrafish redox process, indicating that redox status is critical in the battle between the host and pathogen.ConclusionsAdvancing from the single-species network construction method, the interspecies network construction approach allows further characterization and elucidation of the host-pathogen interactions. With continued accumulation of interspecies transcriptomics data, the proposed method could be used to explore progressive network rewiring over time, which could benefit the development of network medicine for infectious diseases.

Highlights

  • Despite clinical research and development in the last decades, infectious diseases remain a top global problem in public health today, being responsible for millions of morbidities and mortalities each year

  • The identified C. albicans-zebrafish interspecies protein-protein interaction (PPI) network highlights the association between C. albicans pathogenesis and the zebrafish redox process, indicating that redox status is critical in the battle between the host and pathogen

  • On the basis of the time-course gene expression profiles and one-way analysis of variance (ANOVA), 1,728 genes (27.86%) for C. albicans and 680 genes (2.59%) for zebrafish were identified as dynamically regulated genes and their corresponding gene products were selected as target proteins in the protein pool

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Summary

Introduction

Despite clinical research and development in the last decades, infectious diseases remain a top global problem in public health today, being responsible for millions of morbidities and mortalities each year. Many studies have sought to investigate host-pathogen interactions from various viewpoints in attempts to understand pathogenic and defensive mechanisms, which could help control pathogenic infections. Most of these efforts have focused predominately on the host or the pathogen individually rather than on a simultaneous analysis of both interaction partners. The zebrafish model has been used to study human pathogens or closely related animal pathogens, either using adult fish with a fully developed adaptive immune system, or using embryos or larvae that rely solely on innate immunity [13,14]. Zebrafish are suitable for our study characterizing host-pathogen interactions with C. albicans

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