title: Stress adaptation in a pathogenic fungus.
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 non-additive 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.
authors.affiliation: School of Medical Sciences, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen AB25 2ZD, UK.
authors.forename: Alistair J P
authors.initials: AJ
authors.lastname: Brown
authors.forename: Susan
authors.initials: S
authors.lastname: Budge
authors.forename: Despoina
authors.initials: D
authors.lastname: Kaloriti
authors.forename: Anna
authors.initials: A
authors.lastname: Tillmann
authors.forename: Mette D
authors.initials: MD
authors.lastname: Jacobsen
authors.forename: Zhikang
authors.initials: Z
authors.lastname: Yin
authors.forename: Iuliana V
authors.initials: IV
authors.lastname: Ene
authors.forename: Iryna
authors.initials: I
authors.lastname: Bohovych
authors.forename: Doblin
authors.initials: D
authors.lastname: Sandai
authors.forename: Stavroula
authors.initials: S
authors.lastname: Kastora
authors.forename: Joanna
authors.initials: J
authors.lastname: Potrykus
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Ballou
authors.forename: Delma S
authors.initials: DS
authors.lastname: Childers
authors.forename: Shahida
authors.initials: S
authors.lastname: Shahana
authors.forename: Michelle D
authors.initials: MD
authors.lastname: Leach
mesh_terms: D000222:Adaptation, Physiological; D002176:Candida albicans / Q000378:metabolism / Q000472:pathogenicity*; D005656:Fungal Proteins / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D018869:Heat-Shock Response / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009997:Osmotic Pressure / Q000502:physiology*; D018384:Oxidative Stress / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D012568:Schizosaccharomyces / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D005656:Fungal Proteins; D020928:Mitogen-Activated Protein Kinases; D005947:Glucose
keywords: Candida albicans; Carbon metabolism; Cationic stress; Fungal pathogenicity; Heat shock; Nitrosative stress; Osmotic stress; Oxidative stress; Stress adaptation