Dynamic Transcript Profiling of Candida albicans Infection in Zebrafish: A Pathogen-Host Interaction Study

Abstract

Candida albicans is responsible for a number of life-threatening infections and causes considerable morbidity and mortality in immunocompromised patients. Previous studies of C. albicans pathogenesis have suggested several steps must occur before virulent infection, including early adhesion, invasion, and late tissue damage. However, the mechanism that triggers C. albicans transformation from yeast to hyphae form during infection has yet to be fully elucidated. This study used a systems biology approach to investigate C. albicans infection in zebrafish. The surviving fish were sampled at different post-infection time points to obtain time-lapsed, genome-wide transcriptomic data from both organisms, which were accompanied with in sync histological analyses. Principal component analysis (PCA) was used to analyze the dynamic gene expression profiles of significant variations in both C. albicans and zebrafish. The results categorized C. albicans infection into three progressing phases: adhesion, invasion, and damage. Such findings were highly supported by the corresponding histological analysis. Furthermore, the dynamic interspecies transcript profiling revealed that C. albicans activated its filamentous formation during invasion and the iron scavenging functions during the damage phases, whereas zebrafish ceased its iron homeostasis function following massive hemorrhage during the later stages of infection. Most of the immune related genes were expressed as the infection progressed from invasion to the damage phase. Such global, inter-species evidence of virulence-immune and iron competition dynamics during C. albicans infection could be crucial in understanding control fungal pathogenesis.

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“…Epithelial cells play an important role in signaling specific cells to support an immune response to C. albicans (Gratacap et al, 2013). Wherein, C. albicans may colonize the host's epithelial surface and persist on growing resulting in deep penetration into tissues and organs, causing severe damage and probable host mortality (Chen et al, 2013). This explanation was confirmed in our study by appearance of button-like ulcers on the area of the caudal peduncle and cotton wool-like growth on various parts of the body.…”

Host response toCandida albicansbloodstream infection and sepsis

“…and comparative intra-species transcriptional responses of C. albicans. [22][23][24] Notably, the roles of NADPH oxidase in response to C. albicans hyphae have been expanded upon with the help of non-invasive imaging of spacio-temporal macrophage responses in this model. 24 The most commonly used infection model is the mouse, and murine models have been developed to mimic both major routes of C. albicans dissemination.…”

The other white‐nose syndrome transcriptome: Tolerant and susceptible hosts respond differently to the pathogen Pseudogymnoascus destructans

“…Few interactions between fungal pathogens and vertebrate hosts are well understood, and these interactions are most often studied in susceptible species (Chen et al., 2013; Field et al., 2015). Generalizing results from these approaches could limit or misdirect the development of treatments, because pathogen virulence depends on complex interactions between the pathogen, the host, and the environment (James et al., 2015; Perez‐Nadales et al., 2014).…”