G-Protein Signaling Pathways: Regulating Morphogenesis and Virulence of Cryptococcus
This chapter addresses the roles of heterotrimeric and monomeric G proteins in the growth and development of Cryptococcus neoformans. The central motifs of the cAMP signal transduction pathway are highly conserved in eukaryotes, allowing diverse cell types to respond to different environmental stresses. However, the role of this pathway in microbial virulence was not predicted in studies involving nonpathogenic model organisms. Additionally, fungal pathogens of plants, such as the maize pathogen Ustilago maydis and the rice blast fungus Magnaporthe grisea, use cAMP pathways to regulate morphogenesis and virulence. Alternatively, overproduction of intracellular cyclic AMP (cAMP) may also impair virulence through mechanisms such as stress tolerance modulation. Studies of RGS proteins in Cryptococcus have revealed that the regulation of G-protein signaling is more intricate and potentially more complicated than in S. cerevisiae. The C. albicans NRG1 ortholog represses the transcription of several genes required for the yeast-hyphal transition, and this gene is required for Candida virulence. Several of the capsule and melanin genes whose transcription is controlled by cAMP do not appear to be targets of Nrg1. Additionally, the altered capsule phenotype of the nrg1 mutant strain is less severe than the acapsular phenotype of strains with defective cAMP signaling. Lastly, melanin is not significantly altered in the nrg1 mutant. The cAMP signal transduction pathway plays a central role in the stress response and virulence of microbial pathogens. Animal modeling of cryptococcal infection with MATα and MATa strains suggest that MATα strains are intrinsically more virulent.
