Morphological transitions in eukaryotic pathogens are often a key component of virulence. In the opportunistic fungal pathogen Cryptococcus neoformans, changes in cell morphology result in altered host-pathogen interactions and virulence. In response to the host lung environment, Cryptococcus produces enlarged titan cells that can resist phagocytosis. Laura H. Okagaki of the University of Minnesota, Minneapolis, et al. identify the environmental sensing pathway that regulates titan cell formation upon inhalation by the host. "This pathway involves signaling by G-protein coupled receptors via the camp/PKA pathway and the transcription factor Rim101 to modulate cell morphology," says corresponding author Kirsten Nielsen, also of Minnesota. "The PKA pathway is known to regulate the production of virulence factors in C. neoformans, thus our data show that titan cell formation is coregulated with other well-known virulence factors. In addition, we found that the pheromone signaling pathway in C. neoformans has been rewired to allow interaction with pathways affecting pathogenesis. Understanding how titan cells are formed may enable development of new treatment strategies targeting this novel virulence factor."

(L. H. Okagaki, Y. Wang, E. R. Ballou, T. R. O'Meara, Y.-S. Bahn, J. A. Alspaugh, C. Xue, and K. Nielsen. 2011. Cryptococcal titan cell formation is regulated by G-protein signaling in response to multiple stimuli. Eukaryot. Cell 10:1306-1316.)