Funding We are grateful to our funding bodies for their support. This work was supported by the European Commission [FINSysB, PITN-GA-2008-214004; STRIFE, ERC-2009-AdG-249793], by the UK Biotechnology and Biological Research Council [grant numbers BBS/B/06679; BB/C510391/1; BB/D009308/1; BB/F000111/1; BB/F010826/1; BB/F00513X/1], and by the Wellcome Trust [grant numbers 080088, 097377]. M.D.L. was also supported by a Carnegie/Caledonian Scholarship and a Sir Henry Wellcome Postdoctoral Fellowship from the Wellcome Trust [grant number 096072]. Deposited in PMC for immediate release.Peer reviewedPublisher PD

Ballou, Elizabeth R

Bohovych, Iryna

Brown, Alistair J P

Budge, Susan

Childers, Delma S

Ene, Iuliana V

Jacobsen, Mette D

Kaloriti, Despoina

Kastora, Stavroula

Leach, Michelle D

Potrykus, Joanna

Sandai, Doblin

Shahana, Shahida

Tillmann, Anna

Yin, Zhikang

Journal of Experimental Biology

English

PubMed

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

Brown, Alistair J. P.

Jacobsen, Mette D.

Ene, Iuliana V.

Ballou, Elizabeth R.

Childers, Delma S.

Leach, Michelle D.

DigitalCommons@University of Nebraska

Stress adaptation in a pathogenic fungus

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.</p

University of Birmingham Research Portal

UNL | Libraries

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.</jats:p

Alistair J. P. Brown

Susan Budge

Despoina Kaloriti

Anna Tillmann

Mette D. Jacobsen

Zhikang Yin

Iuliana V. Ene

Iryna Bohovych

Doblin Sandai

Stavroula Kastora

Joanna Potrykus

Elizabeth R. Ballou

Delma S. Childers

Shahida Shahana

Michelle D. Leach

Crossref

Funding We are grateful to our funding bodies for their support. This work was supported by the European Commission [FINSysB, PITN-GA-2008-214004; STRIFE, ERC-2009-AdG-249793], by the UK Biotechnology and Biological Research Council [grant numbers BBS/B/06679; BB/C510391/1; BB/D009308/1; BB/F000111/1; BB/F010826/1; BB/F00513X/1], and by the Wellcome Trust [grant numbers 080088, 097377]. M.D.L. was also supported by a Carnegie/Caledonian Scholarship and a Sir Henry Wellcome Postdoctoral Fellowship from the Wellcome Trust [grant number 096072]. Deposited in PMC for immediate release.Peer reviewe

Aberdeen University Research

http://creativecommons.org/licenses/by-nc-sa/3.0

Stress adaptation in a pathogenic fungus

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