Human fungal pathogens are responsible for over 1.6 million deaths and approximately billion of superficial mucosal infections worldwide each year. Aging and respiratory diseases increase the risk of invasive fungal disease that can also lead to severe illness and death. Last year, the World Health Organization (WHO) released a report recommending to ”focus and drive further research and policy interventions to strengthen the global response to fungal infections and antifungal resistance”. Four Candida spp. are highlighted on the released fungal priority list with C. albicans in the most critical group. C. albicans is an opportunistic fungal pathogen. It is found as a commensal in the mouth and gastrointestinal tract in ~ 50% of healthy adults. In specific conditions, the fungus becomes pathogenic, and causes an infection, candidiasis, which results from fungal proliferation. C. albicans, a dimorphic fungus, thrives in either budding or filamentous forms due to a complex interplay of signals and polarity-regulating proteins conserved among eukaryotic cells. Both morphologies coexist in tissues during systemic infection, with filaments promoting tissue invasion and damage, and budding cells facilitating mucosal colonization, dissemination, and biofilm formation. Filamentous growth, conserved in most fungi, comprises tubular filaments that extend and explore surroundings, enabling tissue invasion. The leading filament grows apically, often accompanied by branching to maximize the number of growing filament tips. Branching may occur at cell tips or within subapical compartments, with the latter, called lateral branching, being predominantly observed in C. albicans. Although branching is implicated in fungal virulence, its exact function remains enigmatic.
In this project we aimed to understand filament branching addressing three questions:
1) Is branching distinct from the main filament?
2) Are branches responding differently to antifungal drugs?
3) Is branching important for fungal virulence?
Our results so far show that branching is a distinct developmental state that contributes to the antifungal response and plays a potential role in pathogenicity. Branching is virtually present in all filamentous fungi, including those that has a major impact on our economy. Globally, fungal pathogens cause crop losses of 10-30% (0.1-0.2 trillion €) each year and $7.5 billion of direct medical costs in the U.S.A. alone. Research conducted in BranchOut has provided a major understanding of the so far unknown functions and regulation of branching, and its implication in virulence.
