Abstract：
We used whole-genome sequencing to analyze a collection of 35 fluconazole-resistant and 7 susceptible Candida parapsilosis isolates together with coverage analysis and GWAS techniques to identify new mechanisms of fluconazole resistance. Phylogenetic analysis shows that although the collection is diverse, two persistent clinical lineages were identified. We identified copy number variation (CNV) of two genes, ERG11 and CDR1B, in resistant isolates. Two strains have a CNV at the ERG11 locus; the entire ORF is amplified in one, and only the promoter region is amplified in the other. We show that the annotated telomeric gene CDR1B is actually an artifactual in silico fusion of two highly similar neighboring CDR genes due to an assembly error in the C. parapsilosis CDC317 reference genome. We report highly variable copy numbers of the CDR1B region across the collection. Several strains have increased the expansion of the two genes into a tandem array of new chimeric genes. Other strains have experienced a deletion between the two genes creating a single gene with a reciprocal chimerism. We find translocations, duplications, and gene conversion across the CDR gene family in the C. parapsilosis species complex, showing that it is a highly dynamic family.
摘要：
我们使用全基因组测序分析了35个氟康唑耐药和7个易感的近平滑念珠菌分离株，以及覆盖率分析和GWAS技术，以确定氟康唑耐药的新机制。系统发育分析表明，尽管集合是多样的，确定了两个持续的临床谱系.我们确定了两个基因的拷贝数变异（CNV），ERG11和CDR1B,在抗性分离物中。两个菌株在ERG11基因座处具有CNV;整个ORF被扩增为一个，而另一个只有启动子区被扩增。我们表明，注释的端粒基因CDR1B实际上是两个高度相似的相邻CDR基因的人工计算机融合，这是由于近平滑梭菌CDC317参考基因组中的组装错误。我们报告了整个集合中CDR1B区域的高度可变的拷贝数。几种菌株已经将这两种基因扩展为新嵌合基因的串联阵列。其他菌株经历了两个基因之间的缺失，从而产生了具有相互嵌合体的单个基因。我们发现易位，重复,以及近平滑梭菌物种复合体中CDR基因家族的基因转换，表明这是一个高度动态的家庭。
