Mycobiology.  2009 Sep;37(3):161-170. 10.4489/MYCO.2009.37.3.161.

The Stress-Activated Signaling (SAS) Pathways of a Human Fungal Pathogen, Cryptococcus neoformans

• Jung KW
• Bahn YS

• KMID: 2053008
• DOI: http://doi.org/10.4489/MYCO.2009.37.3.161

Abstract

Cryptococcus neoformans is a basidiomycete human fungal pathogen that causes meningoencephalitis in both immunocompromised and immunocompetent individuals. The ability to sense and respond to diverse extracellular signals is essential for the pathogen to infect and cause disease in the host. Four major stress-activated signaling (SAS) pathways have been characterized in C. neoformans, including the HOG (high osmolarity glycerol response), PKC/Mpk1 MAPK (mitogen-activated protein kinase), calcium-dependent calcineurin, and RAS signaling pathways. The HOG pathway in C. neoformans not only controls responses to diverse environmental stresses, including osmotic shock, UV irradiation, oxidative stress, heavy metal stress, antifungal drugs, toxic metabolites, and high temperature, but also regulates ergosterol biosynthesis. The PKC (Protein kinase C)/Mpk1 pathway in C. neoformans is involved in a variety of stress responses, including osmotic, oxidative, and nitrosative stresses and breaches of cell wall integrity. The Ca2+/calmodulin- and Ras-signaling pathways also play critical roles in adaptation to certain environmental stresses, such as high temperature and sexual differentiation. Perturbation of the SAS pathways not only impairs the ability of C. neoformans to resist a variety of environmental stresses during host infection, but also affects production of virulence factors, such as capsule and melanin. A drug(s) capable of targeting signaling components of the SAS pathway will be effective for treatment of cryptococcosis.

Keyword

Cryptococcus neoformans; Human fungal pathogens; SAS pathways; Signaling; Stress-response

MeSH Terms

Basidiomycota
Calcineurin
Cell Wall
Cryptococcosis
Cryptococcus
Cryptococcus neoformans
Ergosterol
Glycerol
Humans
Melanins
Meningoencephalitis
Osmolar Concentration
Osmotic Pressure
Oxidative Stress
Phenothiazines
Phosphotransferases
Sex Differentiation
Virulence Factors
Calcineurin
Ergosterol
Glycerol
Melanins
Phenothiazines
Phosphotransferases
Virulence Factors