FIGURE 11.

The lead compounds identified in this study address a key clinical need for alternatives to broad spectrum antifungals. Challenge: While still the lead option for the management of microbial infections, broad spectrum growth limiting antifungals are increasingly being challenged by limiting factors including antifungal resistance, the aggressive persistence of known pathogens in a biofilm lifestyle, and the collateral damage caused to the host microbiome leading to dysbiosis, Solution: Exploiting new knowledge of cell–cell communication systems and utilizing synthetic chemistry approaches to generate suites of derivatized compounds, has made possible the development of anti-biofilm small molecules that are selectively non-toxic in mammalian cell lines. These have the potential to lock yeast and fungal pathogens such as A. fumigatus in the non-hyphal state, potentially rendering them more susceptible to immune challenge, and enhancing the effectiveness of conventional antifungal compounds.