Dynamic transcript profiling of Candida albicans infection in zebrafish: a pathogen-host interaction study

Area of Science:

• Mycology
• Infectious Diseases
• Systems Biology

Background:

• Candida albicans causes severe infections, particularly in immunocompromised individuals.
• Pathogenesis involves adhesion, invasion, and tissue damage, but the yeast-to-hyphae transition mechanism remains unclear.
• Understanding C. albicans virulence requires insights into host-pathogen interactions.

Purpose of the Study:

• To elucidate the mechanism triggering Candida albicans transformation during infection using a systems biology approach.
• To analyze dynamic, genome-wide transcriptomic data from C. albicans and zebrafish during infection.
• To correlate gene expression profiles with histological changes to understand infection phases.

Main Methods:

• A systems biology approach was employed to study C. albicans infection in zebrafish.
• Time-lapsed, genome-wide transcriptomic data were collected from both organisms post-infection.
• Principal component analysis (PCA) was used to analyze dynamic gene expression, alongside histological analyses.

Main Results:

• C. albicans infection was categorized into three phases: adhesion, invasion, and damage, supported by histological data.
• C. albicans initiated filamentous growth during invasion and iron scavenging during damage.
• Zebrafish ceased iron homeostasis and experienced hemorrhage during later infection stages, with increased immune gene expression.

Conclusions:

• The study provides global, inter-species evidence of virulence-immune and iron competition dynamics during C. albicans infection.
• Understanding these dynamics, including C. albicans morphological changes and host iron dysregulation, is crucial for controlling fungal pathogenesis.
• This research offers a comprehensive view of host-pathogen interactions in a live infection model.