ena-STUDY-iBiMED - Institute of Biomedicine-26-12-2015-14:03:18:903-282
In this study we tested the hypothesis that generalized codon ambiguity could be beneficial to evolution of resistance against amphotericin B. For this, we have evolved C. albicans strains that incorporate serine at CTA , CTC, CTT (Leucine), ATC (Isoleucine), GCC (Alanine), GGA (Glycine), AAG (Lysine), ACC (Threonine) and TAC (Tyrosine) codons in the presence amphotericin B and characterized them at the genome level. We identified a number of genomic features and key genes that shed new light onto how chimeric tRNAs affects acquisition of resistance to amphotericin B.
Translational errors that occur at high rates influence organism viability decreasing is fitness, however these translational errors can increase proteomic diversity providing an advantageous source of phenotypic variability. Previous studies linked Candida albicans CUG codon ambiguous translation to acquired antifungal resistance. To elucidate how genetic code ambiguity in non CUG codon affects C. albicans genome when this fungus is exposed to antifungal, we have constructed several Serine tRNAs that misincorporate Serine at CTA, CTC, CTT (Leucine), ATC (Isoleucine), GCC (Alanine), GGA (Glycine), AAG (Lysine), ACC (Threonine) and TAC (Tyrosine) codons, expressed them in a laboratory strains of C. albicans and evolved them with increased concentration of antifungal amphotericin B. Genome analysis of these evolved mistranslating strains revealed several SNPs, and common response with SNP detected in gene C3_02410C_A (orf19.229). We hypothesize that this SNPs may decrease Psh1 efficiency, leading to an increase of Cse4 promoting genetic alterations.
Translational errors that occur at high rates influence organism viability decreasing is fitness, however these translational errors can increase proteomic diversity providing an advantageous source of phenotypic variability. Previous studies linked Candida albicans CUG codon ambiguous translation to acquired antifungal resistance. To elucidate how genetic code ambiguity in non CUG codon affects C. albicans genome when this fungus is exposed to antifungal, we have constructed several Serine tRNAs that misincorporate Serine at CTA, CTC, CTT (Leucine), ATC (Isoleucine), GCC (Alanine), GGA (Glycine), AAG (Lysine), ACC (Threonine) and TAC (Tyrosine) codons, expressed them in a laboratory strains of C. albicans and evolved them with increased concentration of antifungal amphotericin B. Genome analysis of these evolved mistranslating strains revealed several SNPs, and common response with SNP detected in gene C3_02410C_A (orf19.229). We hypothesize that this SNPs may decrease Psh1 efficiency, leading to an increase of Cse4 promoting genetic alterations.