Project description:The fungal pathogen Candida albicans and other pathogens of the CTG clade reassigned the leucine CUG codon to serine and tolerate highly variable levels of both serine and leucine at CUG positions in response to environmental cues. Previous studies found that increased leucine misincorporation levels enhance resistance to drugs but the underlying mechanisms are not known. To clarify the biological role of this tuneable codon ambiguity, we evolved C. albicans strains engineered to mistranslate CUG at elevated levels, in the presence and absence of the antifungal drug fluconazole
Project description:The fungal pathogen Candida albicans and other pathogens of the CTG clade reassigned the leucine CUG codon to serine and tolerate highly variable levels of both serine and leucine at CUG positions in response to environmental cues. Previous studies found that increased leucine misincorporation levels enhance resistance to drugs but the underlying mechanisms are not known. To clarify the biological role of this tuneable codon ambiguity, we evolved C. albicans strains engineered to mistranslate CUG at elevated levels, in the presence and absence of the antifungal drug fluconazole
Project description:The leucine CUG codon was reassigned to serine in the fungal pathogen Candida albicans. To clarify the biological role of this tuneable codon ambiguity on drug resistance, we evolved C. albicans strains that were engineered to mistranslate the CUG codon at constitutively elevated levels, in the presence and absence of the antifungal drug fluconazole. Elevated levels of mistranslation resulted in the rapid acquisition of resistance to fluconazole.