Oxidative stress and virulence in Candida albicans

• Main Author: Chaves, Guilherme Maranhão
• Published: University of Aberdeen 2006
• Subjects: 616.969
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.425097

This thesis had the purpose to understand pathogenicity in Candida albicans. The study focused on the previously known virulence factors. In addition, new genes related to virulence were investigated. To achieve this objective, two strains were initially compared; SC5314 (virulent strain) and RV4688 (attenuated strain) by transcript profiling and phenotypic analysis. Transcript profiling revealed that genes related to oxidative stress were down-regulated in the attenuated strain as compared to the virulent strain. RV4688 also formed hypha less readily and adhered less to buccal epithelia than SC5314. It was also determined that the virulence status of these two strains could not be changed. As suggested by microarrays, genes related to oxidative stress might be related to virulence in C. albicans. Therefore, the role of three different genes involved in stress response was analysed: SOD1, SOD2 and TTR1. The D sod1/sodl and D sod2/sod2 mutants were kindly provided by Dr. Sa-Ouk Kang. TTR1 was disrupted and subsequently reintegrated. To investigate the role of two genes in oxidative stress and virulence, a double mutant for SOD1 and TTRI was also generated and each gene was individually reintegrated. The oxidative stress mutants had delayed evagination to form germ tubes. The SOD1 and TTR1 genes seem to have specific roles to respond to the oxidative stress inducers menadione and diamide. However, both of them seem important for virulence in C. albicans, as the D sod1/sod1 and D ttr1/ttr1 mutants were attenuated for virulence in mice and quantitatively more killed by human neutrophils than the wild-type control. When different clinical isolates were characterized, it was demonstrated that SC5314 does not reflect what might happen with all the wild-type virulent strains because other clinical isolates showed clearly different phenotypes. Therefore, C. albicans virulence properties expression might be different in each strain.