Objectives:
For a fungus, there may nothing as biologically variable and highly regulated as its cell wall. This makes the wall challenging to study, but worth the effort because of the potential to reveal novel targets for antifungal drugs and mechanisms that are important for immune recognition. Differences and adaptations of cell wall composition can act to resist chemotherapy and create a moving target for efficient immune recognition.
Methods and materials:
We have used a variety of microscopic, forward and reverse genetic and immunological tools to generate a new spatially accurate model of the cell wall and to explore how dynamic changes in the wall influence drug efficacy and immune surveillance. We also have screened a haploid library of C. albicans mutants with immune pattern recognition receptors (PRRs) to define the sub set of fungal genes that assemble and regulate immune epitopes.
Results:
Our molecular and cellular studies show that the cell has a mechanism to maintain wall robustness within physiological limits and has enabled the components of the wall to be defined with spatial precision. We have also demonstrated that immune relevant epitopes can be diffuse or clustered, superficial or buried in the cell wall and they changed during batch culture and between yeast, hypha and other cellular morphologies. Unbiased screening of a haploid mutant library has revealed gene sets for both predicted (e.g. cell wall glycosylation) and novel processes (I’ll reveal these in my talk) that are important for the assembly of the cell wall immune epitope.
Conclusion:
These experiments demonstrate that the fungal cell surface is ordered, complex and dynamically changing, requiring immune recognition to integrate information from the surveillance of multiple receptors operating singly and in combination. My presentation will focus on work that demonstrates that describes recent advances that have generated a scaler and dynamic model of the cell wall that illuminates mechanisms of immune recognition and cell wall homeostasis.
Reference: Gow, N.A.R. & Lenardon, M.D. (2022). Architecture the dynamic fungal cell wall. Nature Reviews Microbiology https://doi.org/10.1038/s41579-022-00796-9. PMID 36266346