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

Poster number: 01
Glucose promotes oxidative stress resistance in Candida
albicans via specific signalling pathways
Iryna Bohovych 1 , Pedro Miramón 2 , Aaron Mitchell 3 , Bernhard Hube 2 ,
Alistair JP Brown 1
1 Aberdeen Fungal Group, School of Medical Sciences, University of Aberdeen, Foresterhill,
Aberdeen AB25 2ZD, UK; 2 Microbial Pathogenicity, Hans Knoell Institute, Beutenbergstraße
11a, Jena 07745, Germany; 3 Department of Biological Sciences, Carnegie Mellon University,
Pittsburgh, Pennsylvania 15213, USA
Candida albicans, a successful human pathogen, displays the phenomenon of
glucose-enhanced oxidative stress resistance (Rodaki et al., 2009), which is not
observed in other yeast species tested. The molecular mechanisms that mediate
glucose-enhanced oxidative stress resistance in C. albicans are not clear. We
reasoned that glucose signalling might play a major role. Therefore we tested the
impact of specific C. albicans mutations to determine which of known signalling
pathways are required for glucose-enhanced oxidative stress resistance.
The Sugar Receptor-Repressor (Hgt4-Rgt1) pathway, homologous to the Rgt2/Snf3
pathway in S. cerevisiae, is not required for the phenotype. In contrast, a snf1
mutant, which lacks a key component of the Glucose Repression Pathway,
displayed high oxidative stress resistance on lactate, not altered by glucose. A kis1
mutant, lacking one of the subunits of Snf1 complex, displayed a related phenotype.
The data indicate that in the absence of glucose the Glucose Repression Pathway
represses glucose-enhanced oxidative stress resistance.
cAMP signalling also appears to play a role in glucose-enhanced oxidative stress
resistance. This phenotype was repressed by exogenous dibutyryl cAMP and by a
pde2 mutation that is thought to increase intracellular cAMP levels. Also the
phenotype was enhanced by inactivation of adenylyl cyclase (cyr1).
Having shown that both cAMP signalling and the Glucose Repression Pathway play
important roles in mediating glucose-enhanced stress resistance, the next step was
to identify targets of these pathways that might contribute to the phenotype.
Comparative analyses of transcriptomic profiles of C. albicans glucose- and lactategrown
cells in response to oxidative stress and glucose treatment correspondingly
revealed a small set of commonly up-regu lated genes (Enjalbert et al., 2006; Rodaki
et al., 2009). The impact of the cAMP and Glucose Repression pathways on these
genes is being determined.
We are grateful to the European Commission for funding the FINSysB Marie Curie Initial Training Network
(PITN-GA-2008-214004).
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