Revisiting Old Questions and New Approaches to Investigate the Fungal Cell Wall Construction

The beginning of our understanding of the cell wall construction came from the work of talented biochemists in the 70-80's. Then came the era of sequencing. Paradoxically, the accumulation of fungal genomes complicated rather than solved the mystery of cell wall construction, by revealing the involvement of a much higher number of proteins than originally thought. The situation has become even more complicated since it is now recognized that the cell wall is an organelle whose composition continuously evolves with the changes in the environment or with the age of the fungal cell. The use of new and sophisticated technologies to observe cell wall construction at an almost atomic scale should improve our knowledge of the cell wall construction. This essay will present some of the major and still unresolved questions to understand the fungal cell wall biosynthesis and some of these exciting futurist approaches. What is our current knowledge in the understanding of the fungal cell wall biosynthesis in 2020? Many contributors to the Current Topics in Microbiology and Immunology issue entitled "The fungal cell wall. An armor and a weapon for human fungal pathogens" have presented the state of the art of our knowledge on the structural organization, biosynthesis, and biological function of the cell wall of the human fungal pathogens. Here, we present some of the still unresolved but essential questions in the area. Questions are focused on human pathogenic fungi but will be comparatively assessed with plant cell wall and fungal models. We also hope that new methodologies presented at the end of this report will inspire the development of new approaches absolutely required to advance the fungal cell wall field.