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Integrative Model of Oxidative Stress Adaptation in the Fungal Pathogen Candida albicans

Lookup NU author(s): Professor Janet Quinn



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


The major fungal pathogen of humans, Candida albicans, mounts robust responses to oxidative stress that are critical for its virulence. These responses counteract the reactive oxygen species (ROS) that are generated by host immune cells in an attempt to kill the invading fungus. Knowledge of the dynamical processes that instigate C. albicans oxidative stress responses is required for a proper understanding of fungus-host interactions. Therefore, we have adopted an interdisciplinary approach to explore the dynamical responses of C. albicans to hydrogen peroxide (H2O2). Our deterministic mathematical model integrates two major oxidative stress signalling pathways (Cap1 and Hog1 pathways) with the three major antioxidant systems (catalase, glutathione and thioredoxin systems) and the pentose phosphate pathway, which provides reducing equivalents required for oxidative stress adaptation. The model encapsulates existing knowledge of these systems with new genomic, proteomic, transcriptomic, molecular and cellular datasets. Our integrative approach predicts the existence of alternative states for the key regulators Cap1 and Hog1, thereby suggesting novel regulatory behaviours during oxidative stress. The model reproduces both existing and new experimental observations under a variety of scenarios. Time-and dose-dependent predictions of the oxidative stress responses for both wild type and mutant cells have highlighted the different temporal contributions of the various antioxidant systems during oxidative stress adaptation, indicating that catalase plays a critical role immediately following stress imposition. This is the first model to encapsulate the dynamics of the transcriptional response alongside the redox kinetics of the major antioxidant systems during H2O2 stress in C. albicans.

Publication metadata

Author(s): Komalapriya C, Kaloriti D, Tillmann AT, Yin ZK, Herrero-de-Dios C, Jacobsen MD, Belmonte RC, Cameron G, Haynes K, Grebogi C, de Moura APS, Gow NAR, Thiel M, Quinn J, Brown AJP, Romano MC

Publication type: Article

Publication status: Published

Journal: PLOS ONE

Year: 2015

Volume: 10

Issue: 9

Online publication date: 14/09/2015

Acceptance date: 20/08/2015

Date deposited: 22/10/2015

ISSN (electronic): 1932-6203

Publisher: Public Library of Science


DOI: 10.1371/journal.pone.0137750

PubMed id: 26368573


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Funder referenceFunder name
CRISP project (Combinatorial Responses In Stress Pathways)
080088Wellcome Trust
097377Wellcome Trust
BB/F00513X/1UK Biotechnology and Biological Research Council
BB/F005210/1-2UK Biotechnology and Biological Research Council
ERC-2009-AdG-249793European Research Council