Host-pathogen interaction networks between Candida albicans and zebrafish: the dynamics of iron and glucose

Abstract

Candida albicans is a commensal diploid fungus that could cause opportunistic oral and genital infections in humans. Though benign for immunocompetent humans, systemic fungal infections of C. albicans have become major causes of morbidity and mortality in immunocompromised patients. As a result, the understanding of the dynamics of C. albicans pathogenesis and its interaction with the host has emerged as an important topic of study. However, relatively little is known about the host-pathogen interaction networks and the corresponding evolution of the networks across different stages of infection. In this study, we were able to construct the host-pathogen interaction networks between C. albicans and zebrafish for three different infection stages, i.e., the adhesion, the invasion, and the damage stage. Iron is an essential element for both pathogen and host, and intense competition for this precious metal between host and pathogen often occurs during infection. In addition, glucose has been identified as an important resource during hyphae formation, which is highly related to the invasion of pathogen during infection. So we focused on the construction of the interaction networks associated with iron and glucose. From the two resulting interaction networks, we identified highly connected hub genes that are relevant to iron competition or glucose metabolism during infection; distinguished pertinent genes whose connectivity change significantly from stage to stage; and studied the behaviors of these genes that are differentially regulated during different infection stages. The constructed host-pathogen interaction networks for three infection stages provide significant insights into the dynamic regulation for iron competition and glucose metabolism during infection. In fact, based on these interaction networks, we were able to predict the progress of iron competition and glucose metabolism activities throughout the adhesion, invasion, and damage stage. Interestingly, it seems that both C. albicans and zebrafish are more actively involved in the regulation of iron-related genes and proteins during the adhesion stage. During the invasion stage, however, both host and pathogen turn on the regulation of glucose-related genes and proteins. In the last stage of damage, regulatory activities of host and pathogen focus back on iron-related genes and proteins.