Molecular analysis of a glycolytic gene and the effects of glucose on Candida albicans

• Main Author: Rodaki, Alexandra
• Published: University of Aberdeen 2006
• Subjects: 616.969
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.439914

The human fungal pathogen <i>Candida albicans </i>(<i>C. albicans</i>) shows considerable flexibility in adapting to environmental change.  <i>C. albicans </i>cells have evolved various defences, including specific stress responses, to evade the human immune system.  This study explored the relationship between central carbon metabolism and adaptational responses of <i>C. albicans.</i> The first aim was to assess the attractiveness of Fbal as an antifungal target.  <i>C. albicans </i>Fructose-1,6-bisphosphate aldolase (Fbal) is an essential metabolic enzyme required for both glycolysis and gluconeogenesis.  A conditional <i>MET3-FBA1/fba1 </i>mutant was used to assess the role that Fbal plays in the growth and virulence of <i>C. albicans.  </i>This revealed that Fbal enzyme levels must be reduced to less than 15% of wild type levels before the growth of this figures is inhibited.  Furthermore, Fbal depletion was shown to have a fungistatic, rather than a fungicidal effect upon <i>C. albicans </i>growth.  Also, the virulence of the <i>MET3-FBA1/fba1 </i>conditional mutant strain was only partially attenuated in the murine model of systemic candidiasis.  Hence, Fba1 is  not a particularly attractive antifungal target. The second aim was to study the effects of glucose on the <i>C. albicans </i>transcriptome, and to compare these with the corresponding glucose responses of <i>S. cerevisiae.  C. albicans </i>cells exhibited a subtly different transcriptional response to glucose compared with <i>S. cerevisiae.  </i>The responses of central metabolic genes to glucose were similar in these yeasts.  However, specific stress-responsive genes were up-regulated in <i>C. albicans </i>in response to glucose, and this was reflected in corresponding changes in stress resistance.  Thus, glucose responses are linked to certain stress responses in <i>C. albicans.  </i>This may contribute to the success of this fungus as a human pathogen.