Signal Transduction Cascades Regulating Fungal Development and Virulence

Abstract

SUMMARY Cellular differentiation, mating, and filamentous growth are regulated in many fungi by environmental and nutritional signals. For example, in response to nitrogen limitation, diploid cells of the yeast Saccharomyces cerevisiae undergo a dimorphic transition to filamentous growth referred to as pseudohyphal differentiation. Yeast filamentous growth is regulated, in part, by two conserved signal transduction cascades: a mitogen-activated protein kinase cascade and a G-protein regulated cyclic AMP signaling pathway. Related signaling cascades play an analogous role in regulating mating and virulence in the plant fungal pathogen Ustilago maydis and the human fungal pathogens Cryptococcus neoformans and Candida albicans. We review here studies on the signaling cascades that regulate development of these and other fungi. This analysis illustrates both how the model yeast S. cerevisiae can serve as a paradigm for signaling in other organisms and also how studies in other fungi provide insights into conserved signaling pathways that operate in many divergent organisms.

Decreased expression of 14-3-3 inParacoccidioides brasiliensisconfirms its involvement in fungal pathogenesis

“…46 MendesGiannini et al 47 observed a relationship between virulence and adherence to the ECM when comparing several P. brasiliensis isolates that showed different levels of virulence in vivo; the authors demonstrated that the isolate Pb18, which was recently isolated from an animal, had a greater ability to adhere to ECM components. Confirming the results of Andreotti et al, 2005, 27 we demonstrated that low expression of Pb14-3-3 resulted in a reduction of binding to laminin; this interaction was assessed by ELISA, which has greater sensitivity and specificity than the immunoblotting that was performed in the study cited above.…”

Comparative genomics of MAP kinase and calcium–calcineurin signalling components in plant and human pathogenic fungi

“…Core elements of MAPK and calcium signalling pathways are required for virulence in a wide array of fungal pathogens of plants and mammals (Kraus and Heitman, 2003;Lee et al, 2003;Lengeler et al, 2000;Zhao et al, 2007). Such a degree of functional conservation is remarkable, considering the taxonomic and biological diversity among these pathogens, but also raises a number of questions regarding the specific role of these pathways in fungal infection.…”

Mutant alleles of the essential 14-3-3 gene in Candida albicans distinguish between growth and filamentation

“…In C. albicans, filamentation is also induced under nitrogenstarvation conditions and by activation of MAPK and PKA pathways. However, unlike S. cerevisiae, in addition to nutrient starvation multiple in vitro conditions can induce filamentation, including pH, temperature, serum and embedment in agar (reviewed by Berman & Sudbery, 2002;Brown, 2002;Lengeler et al, 2000). In this study several induction methods were tested and Bmh1p was involved in all instances.…”