Candida Infection Biology – fungal armoury, battlefields ... - FINSysB

Survival in the host –mechanisms underlying responses to
oxidative stress in the human pathogen Candida albicans
Alessandra da Silva Dantas 1 , Miranda Patterson 1 , Deborah Smith 1 ,
Catherine Bruce 1 , Donna MacCallum 2 , Lars Erwig 3 , Brian Morgan 1 &
Jan Quinn 1
1Institute for Cell and Molecular Biosciences, Faculty of Medical Sciences, Newcastle
University, Newcastle upon Tyne, NE2 4HH, United Kingdom; 2Aberdeen Fungal Group,
Institute of Medical Sciences, University of Aberdeen, Aberdeen, AB25 2ZD, United Kingdom;
3Division of Applied Medicine, Institute of Medical Sciences, University of Aberdeen,
Aberdeen, AB25 2ZD, United Kingdom.
The ability of the major systemic fungal pathogen of humans, Candida albicans, to
sense and respond to reactive oxygen species (ROS) such as H 2 O 2 , generated by
the host immune system, is essential for survival in the host. This oxidative stress
response at the transcriptional level is regulated largely by the AP-1-like
transcription factor Cap1 and, to a lesser extent, the Hog1 stress-activated protein
kinase (SAPK). In addition, H 2 O 2 treatment of C. albicans stimulates the formation
of hyperpolarized buds in a mechanism that requires activation of the Rad53
checkpoint kinase. However, despite strong links between filamentous growth,
responses to ROS, and virulence, remarkably little is known about the intracellular
signalling mechanisms that regulate the activation of such H 2 O 2 -responsive
signalling pathways in C. albicans. During this talk I will present recent work from
my group which has investigated the mechanisms underlying oxidative stressmediated
activation of both the Cap1 transcription factor, and the Hog1 and Rad53
stress responsive kinases. Whilst the Saccharomyces cerevisiae paradigm has
provided important insight into oxidative stress signalling mechanisms, our studies
have revealed new circuitry, novel players and unexpected mechanisms in the
medically relevant pathogen C. albicans.
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