Since fungi are eukaryotic and evolved in close association with their mammalian hosts, most essential fungal molecular targets for drug development bear a considerable risk of cross-target host toxicity. The current arsenal of antifungal drugs and therapies are limited in number and diversity, and their efficacy is severely hampered by host toxicity, fungistatic rather than fungicidal activity and drug resistance. our overarching goal is to identify novel fungal-specific targets for the development of fungal-selective, pan-antifungal drugs. To reduce our reliance on pathogen-targeted agents, we propose an integrated approach that will combine therapeutic interventions to boost hosts’ anti-fungal immune response and selective targeting of fungal essential pathways.
Visualizing infection outcome at single-cell resolution
The interaction of microbes with the immune system is multifactorial and depends not only on microbial features but also on the immune state of the host and on environmental factors. The outcome of each individual encounter is context-dependent. Additionally, the microbial and host cell populations are incredibly heterogeneous, which may have significant phenotypic consequences leading to diverse outcomes upon encounter of fungal conidia with immune cells.
We are trying to define how all these components work together to determine the outcome of the interaction, or in other words, what makes a microbe a pathogen?
We have developed a suite of fluorescent probes that enable tracking of these intricate interactions at single-cell resolution, and assessment of the physiological state of the fungus and immune cells in the host tissue.