Stress adaptation in a pathogenic fungus

Authors

Alistair J. P. Brown, University of AberdeenFollow
Susan Budge, University of Aberdeen
Despoina Kaloriti, University of Aberdeen
Anna Tillmann, University of Aberdeen
Mette D. Jacobsen, University of Aberdeen
Zhikang Yin, University of Aberdeen
Iuliana V. Ene, Brown University
Iryna Bohovych, University of Nebraska- LincolnFollow
Doblin Sandai, Universiti Sains Malaysia
Stavroula Kastora, University of Toronto
Joanna Potrykus, University of Toronto
Elizabeth R. Ballou, University of Toronto
Delma S. Childers, University of Toronto
Shahida Shahana, University of Toronto
Michelle D. Leach, University of Toronto

Date of this Version

2014

Citation

The Journal of Experimental Biology (2014) 217, 144-155 doi:10.1242/jeb.088930

Comments

© 2014. Published by The Company of Biologists Ltd

Abstract

Candida albicans is a major fungal pathogen of humans. This yeast is carried by many individuals as a harmless commensal, but when immune defences are perturbed it causes mucosal infections (thrush). Additionally, when the immune system becomes severely compromised, C. albicans often causes life-threatening systemic infections. A battery of virulence factors and fitness attributes promote the pathogenicity of C. albicans. Fitness attributes include robust responses to local environmental stresses, the inactivation of which attenuates virulence. Stress signalling pathways in C. albicans include evolutionarily conserved modules. However, there has been rewiring of some stress regulatory circuitry such that the roles of a number of regulators in C. albicans have diverged relative to the benign model yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe. This reflects the specific evolution of C. albicans as an opportunistic pathogen obligately associated with warm-blooded animals, compared with other yeasts that are found across diverse environmental niches. Our understanding of C. albicans stress signalling is based primarily on the in vitro responses of glucose-grown cells to individual stresses. However, in vivo this pathogen occupies complex and dynamic host niches characterised by alternative carbon sources and simultaneous exposure to combinations of stresses (rather than individual stresses). It has become apparent that changes in carbon source strongly influence stress resistance, and that some combinatorial stresses exert nonadditive effects upon C. albicans. These effects, which are relevant to fungus–host interactions during disease progression, are mediated by multiple mechanisms that include signalling and chemical crosstalk, stress pathway interference and a biological transistor.