| Summary: | 碩士 === 國立清華大學 === 生物資訊與結構生物研究所 === 100 === Candida albicans is a major fungal human pathogen, it exists as a commensal organism on the cutaneous and mucosal surfaces of healthy individuals, but in immuno-compromised patients, C. albicans is responsible for a number of life-threatening infections, causing considerable morbidity and mortality. Previous studies of C. albicans pathogenesis have suggested several steps which may lead to mucosal infection, including early adhesion, invasion, and late tissue damage. However, it is difficult to monitor these events in real time in the traditional mouse model system.
In our previous study, we have established a novel zebrafish model for C. albicans infection study. We found C. albicans infection in zebrafish can also be staged into “adhesion’, “invasion”, and “damage”, which are comparable to the findings observed in the mouse model. We then analyzed the dynamic gene expression profiles of C. albicans and zebrafish during pathogen-host interaction. The results indicated that C. albicans activated its iron scavenging function during invasion and damage phases; whereas zebrafish appeared to cease the iron homeostasis function followed by massive hemorrhage toward the damage stage of infection. This suggested iron competition between the zebrafish host and fungal pathogen might be important for the emergence and progression of C. albicans virulence. To verify this, we administrated excessive iron in low pH condition into the microenvironment of the infection site. We observed significant delay in the progression of C. albicans hyphae formation, consequently, zebrafish survival time was prolonged. Nevertheless, we later found the virulence of C. albicans mostly associated with the microenvironmental pH. The addition of iron supplement only has a minor effect in reducing C. albicans’s virulence.
In addition to resource competition, we also examined the host immune responses against the fungal pathogen. From our microarray data, we identified a set of immune related genes that were up-regulated in the zebrafish during C. albicans infection. Furthermore, we found the host adaptive immunity can help zebrafish defense itself from repeated C. albicans infection. Taken together, we showed zebrafish system can be used in studying human fungal infection disease, and might e useful in developing anti- vaccines for commercial fishes in aquaculture.
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