Molecular characterisation of the effects of classical chemotherapy on Candida albicans and systemic candidiasis
Due to chemotherapy-induced immunosuppression and epithelial barrier disruption, cancer patients are well-known to be at increased risk of opportunistic infection, such as those caused by the dimorphic fungus Candida albicans. While effects of chemotherapy on the host are well documented, little is...
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| Format: | Theses and Dissertations |
| Language: | English |
| Published: |
2017
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| Online Access: | http://hdl.handle.net/10356/72226 |
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| Institution: | Nanyang Technological University |
| Language: | English |
| Summary: | Due to chemotherapy-induced immunosuppression and epithelial barrier disruption, cancer patients are well-known to be at increased risk of opportunistic infection, such as those caused by the dimorphic fungus Candida albicans. While effects of chemotherapy on the host are well documented, little is known about direct effects of chemotherapy on the pathogen. We hypothesise that chemotherapeutic agents enhance genomic variation and evolvability in C. albicans colonising the host, thus potentially altering its virulence and its response to antifungal drugs. Here we found that hydroxyurea (HU) induces aneuploidy in C. albicans, and in particular trisomy of Chromosome 2. This aneuploidy not only conferred HU resistance, but also cross-resistance to caspofungin, a first-line antifungal drug. Therefore, chemotherapeutic drugs might negatively impact the outcome of fungal infections not only by suppressing the host’s defence mechanisms but also by generating genomic variation and promoting antifungal drug resistance in a major fungal colonizer of humans.
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