Bergin Sean, Doorley Laura A, Rybak Jeffrey M, Wolfe Kenneth H, Butler Geraldine, Cuomo Christina A, Rogers P David
School of Biomolecular and Biomedical Science, Conway Institute, University College Dublin, Belfield, Dublin, Ireland.
Department of Pharmacy and Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Antimicrob Agents Chemother. 2024 Jun 5;68(6):e0161923. doi: 10.1128/aac.01619-23. Epub 2024 May 7.
We used whole-genome sequencing to analyze a collection of 35 fluconazole-resistant and 7 susceptible 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, and , in resistant isolates. Two strains have a CNV at the 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 is actually an artifactual fusion of two highly similar neighboring genes due to an assembly error in the CDC317 reference genome. We report highly variable copy numbers of the 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 gene family in the species complex, showing that it is a highly dynamic family.
我们使用全基因组测序分析了35株氟康唑耐药菌株和7株敏感菌株，并结合覆盖度分析和全基因组关联研究（GWAS）技术来确定氟康唑耐药的新机制。系统发育分析表明，尽管该菌株集合具有多样性，但仍鉴定出两个持续存在的临床谱系。我们在耐药菌株中鉴定出两个基因的拷贝数变异（CNV）。两株菌株在该位点存在CNV；一株中整个开放阅读框（ORF）被扩增，另一株中仅启动子区域被扩增。我们发现注释的端粒基因实际上是由于CDC317参考基因组组装错误导致的两个高度相似的相邻基因的人为融合。我们报告了该菌株集合中该区域的拷贝数高度可变。几株菌株增加了这两个基因扩展为新的嵌合基因串联阵列。其他菌株在这两个基因之间发生了缺失，形成了一个具有相互嵌合现象的单一基因。我们在该物种复合体的基因家族中发现了易位、重复和基因转换，表明它是一个高度动态的家族。
