A project undertaken at Australia National University, and supervised by Megan Outram
Chytridiomycosis, caused by the chytrid fungus Batrachochytrium dendrobatidis (Bd), is one of the deadliest wildlife diseases ever recorded (Figure 1). It has driven the extinction of over 90 frog species and caused severe population declines in more than 500 others worldwide. Bd attacks the frog’s skin, a vital organ for breathing and regulating water and salt, leading to electrolyte imbalance, cardiac arrest, and death.
Figure 1: Left panel; Southern Corroboree Frog which is highly susceptible to chytridiomycosis. Middle panel; Batrachochytrium dendrobatidis (Bd) zoosporangia. Right panel; Protein gel showing purified antibodies.
In fungal and oomycete pathogens, virulence proteins known as effectors play key roles in infection which function to create an environment for pathogen growth and colonisation. Genomic studies suggest Bd has acquired similar effectors, but none have been experimentally validated or studied for their role in Bd infection and colonisation. As such, the identity and function of these effectors remain largely unknown. In Bd these proteins likely play roles in attaching to frog cells, breaking down skin layers, suppressing the frog’s immune response, or inducing cell death in frog cells. An understanding of the frog chytrid fungus effectors crucial for infection provides opportunities to develop target-based approaches to more effectively combat Bd and safeguard the future of amphibian diversity.
In this project, we aim to identify Bd effectors and to understand their roles in chytrid fungus infection. We will use artificial intelligence-driven protein structure prediction to identify Bd effectors based on three-dimensional similarities to fungal and oomycete effectors. Using different protein expression systems, we will produce recombinant versions of these effectors and determine their protein architecture. Visualisation of their three-dimensional structures will allow us to design highly specific binders to block the function of these effectors in chytrid infection (Figure 1).
By identifying Bd effectors and uncovering the mechanisms driving chytrid infection, this project is a key step toward targeted interventions for chytridiomycosis.