P7 Banging your head against the (fungal) wall

PLENARY SESSION 7, SEPTEMBER 23, 2022, 2:00 PM - 3:00 PM: : For a fungus, there may be nothing as biologically variable and highly regulated as its cell wall. This makes the wall intellectually and methodologically challenging to study, but worth the effort because they have the potential to reveal novel targets for antifungal drugs and the mechanisms that are important for immune recognition. Differences and adaptations to the cell wall composition can serve to resist chemotherapy and create a moving target for efficient immune recognition. 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 show that the cell has a mechanism to maintain wall robustness within physiological limits. We also have 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. We have screened libraries of mutants with immune pattern recognition receptors (PRRs) to define the sub-set of fungal genes that assemble and regulate immune epitopes. This is revealing novel processes that are important for the assembly of the cell wall. These experiments demonstrate that the fungal cell surface is ordered, complex and dynamically changing, requiring immune recognition to mobilize the concerted action of multiple receptors operating singly and in combination. My presentation will focus on work that demonstrates and 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.