Candida albicans, a successful human pathogen, displays the phenomenon of glucoseenhanced oxidative stress resistance (Rodaki et al., 2009), which is not observed in other yeast species tested. The molecular bases of the phenomenon are not clear. It was suggested that glucose signalling might play a major role. Therefore, the impact of specific C. albicans mutations was tested to determine which of three known major glucose signalling pathways are required for glucose-enhanced oxidative stress resistance. Two major glucose signalling pathways were found to contribute to the phenomenon (the glucose repression pathway and the cAMP pathway), and a third pathway (the SRR pathway) is not essential for this response. The next step was to identify targets of these pathways that might contribute to the phenotype. First, it was tested whether known oxidative stress systems contribute to the GEXSR. The selected targets represented almost all main systems involved in redox control and ROS detoxification (catalase, superoxide dismutases, thiredoxins, and glutathione peroxidases) which seemed to contribute not significantly to the GEXSR. The exceptions to this were glutathione reductase (Glr1) and glutaredoxin (Grx2/Ttr1), inactivation of which affected manifestation of the phenomenon. This reinforced the view that the GSH/GSSG balance plays a key role in the GEXSR. Second, 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-regulated genes: UCF1, RNR22, MOH1, orf19.3302, and HSP21/orf19.822 (Enjalbert et al., 2006; Rodaki et al., 2009). Each potential GEXSR-specific gene appeared to be regulated in a distinct manner by the major glucose signalling pathways. The ectopic expression of potential GEXSR targets did not provide any experimental evidence to support their roles in this response. That might be related to inefficient expression from ACT1 promoter under the experimental conditions tested, and also caused by other effects.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:558668 |
| Date | January 2012 |
| Creators | Bohovych, Iryna M. |
| Publisher | University of Aberdeen |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=186766 |
Page generated in 0.0019 seconds