Role of morphogenesis in human fungal pathogens

Abstract

There are uncountable examples of morphogenetic processes in nature. In particular, fungi respond to a set of inductive cues (internal/external) whose outcome is a change of shape and/or size. My latest work has been focused on deciphering the molecular mechanisms involved in different morphogenetic programs, specifically I will show you my work on Cryptococcus neoformans and Candida albicans, two of the main human fungal pathogens.
Cryptococcus neoformans is an opportunistic, round shape, encapsulated fungal pathogen that has a significant incidence among HIV+ patients. This yeast forms Titan cells during infection, which pose a major problem for the immune system and unknown consequences for the development of the disease. Titan cells involved a massive change of size, but keeping its spherical shape. Until last year, research on Titan cells had been hampered by the need of obtaining them from animal models. However, we have described in vitro conditions that promote the transition from regular to titan-like cells which for sure will help to understand the basis of their formation and their role during infection.
On the other hand, Candida albicans is a human commensal that undergoes a mophogenetic switch from yeast form to an invasive filamentous form, which makes it an ideal model to study morphogenesis involving a change of shape. During filamentation, a great number of proteins are located at the tip of the filament and they are secreted or incorporated to the cell wall of the growing filament. Therefore, membrane traffic is a key factor during C. albicans morphogenesis. In particular, my interest was focused on the two independent pools of PI(4)P generated at the Golgi and at the plasma membrane. Keeping the levels of PI(4)P at Golgi and at the plasma membrane is critical for Candida albicans filamentation. In addition, both pools of PI(4)P seem to have important functions during trafficking and response to different stresses, which in turn, could be necessary for the development of the disease.
In conclusion, morphological transitions are critical for fungi to adapt to different environments and survive in the host. The capacity to undergo these transitions allow them to evade the host immune system and therefore contribute to the establishment of the disease. Research on the molecular mechanisms involved in these changes will allow us to better design drug targets and to understand the development of the infection.