Linking morpgology/virulence and drug resistance via ergosterol biosynthesis and glycolysis pathways in Candida albicans

Autor: Ting-Yin Hsiao, 蕭婷尹
Rok vydání: 2006
Druh dokumentu: 學位論文 ; thesis
Popis: 94
Candida albicans is an opportunistic fungal pathogen in humans. It has been reported that the cph1/cph1 efg1/efg1 double mutant of C. albicans is defective in filamentous growth and is also avirulent in a mouse model. The ability of C. albicans to switch between a yeast form and a filamentous form has been implicated in its virulence. Previous comparative genomics studies have profiled the expression differences between the wide-type and the cph1/cph1 efg1/efg1 double mutant strains by the method of Suppression Subtractive Hybridization (SSH) and sequence analysis. Two ergosterol genes, ERG3 and ERG11, were isolated. Mutations in ERG3 or ERG11 can alter the susceptibility of antifungal drugs in Candida albicans. Therefore, the first aim of this study was to investigate the coordination of morphogenesis/ virulence and drug resistance via ergosterol biosynthesis genes. The mRNA expression levels of these two genes were assessed by northern blot analysis. The results shown that the mRNA levels of ERG3 and ERG11 were higher in the cph1/cph1 efg1/efg1 double mutant and CPH1/CPH1 efg1/efg1 mutant than that in the wild-type cells, suggesting a negative regulation of ERGs by EFG1. And it has been proven that in addition to virulence, Efg1 was also involved in drug resistance by negatively regulating ERG3 of the ergosterol biosynthesis pathway in C. albicans. Furthermore a previous study has shown that ENO1、TPI1、GPM1、PYK1and PGK1 of glycolytic genes expressed differently in cph1/cph1 efg1/efg1 double mutant and in wide-type strain. Thus, investigating the linkage of morphogenesis/virulence and drug resistance via glycolysis genes was the other purpose of this study. The results indicated that the expressions of TPI1, GPM1, PYK1 and PGK1 could be affected by the presence of goat serum and antifungal drug. Besides, TPI1 gene was subjected to genetic study by introduction of tetracycline-regulated system. These results indicated that TPI1 gene was associated with morphogenesis and also involved in cell growth. Whether TPI1 gene is involved in drug resistance will require further studies.
Databáze: Networked Digital Library of Theses & Dissertations
Externí odkaz: