Molecular Microbiology and Immunology Department, Brown University, Providence, RI 02912.
Institut Pasteur Bioinformatic Hub, Université Paris Cité, Paris 75015, France.
Proc Natl Acad Sci U S A. 2023 Mar 14;120(11):e2218163120. doi: 10.1073/pnas.2218163120. Epub 2023 Mar 9.
Aneuploidy is a frequent occurrence in fungal species where it can alter gene expression and promote adaptation to a variety of environmental cues. Multiple forms of aneuploidy have been observed in the opportunistic fungal pathogen which is a common component of the human gut mycobiome but can escape this niche and cause life-threatening systemic disease. Using a barcode sequencing (Bar-seq) approach, we evaluated a set of diploid strains and found that a strain carrying a third copy of chromosome (Chr) 7 was associated with increased fitness during both gastrointestinal (GI) colonization and systemic infection. Our analysis revealed that the presence of a Chr 7 trisomy resulted in decreased filamentation, both in vitro and during GI colonization, relative to isogenic euploid controls. A target gene approach demonstrated that , encoding a negative regulator of filamentation located on Chr 7, contributes to increased fitness of the aneuploid strain due to inhibition of filamentation in a gene dosage-dependent fashion. Together, these experiments establish how aneuploidy enables the reversible adaptation of to its host via gene dosage-dependent regulation of morphology.
非整倍体是真菌物种中经常发生的现象，它可以改变基因表达并促进对各种环境线索的适应。在机会性真菌病原体 中观察到多种形式的非整倍体，它是人类肠道微生物组的常见组成部分，但可以逃避这种生态位并导致危及生命的全身性疾病。使用条形码测序 (Bar-seq) 方法，我们评估了一组二倍体 菌株，发现携带第 7 号染色体 (Chr) 三倍体的菌株在胃肠道 (GI) 定植和全身感染期间与更高的适应性相关。我们的分析表明，与同基因的整倍体对照相比，Chr 7 三体的存在导致体外和 GI 定植期间丝状形成减少。靶基因方法表明， 编码位于 Chr 7 上的丝状形成负调节剂的基因，由于丝状形成在基因剂量依赖性方式下受到抑制，导致非整倍体菌株的适应性增加。这些实验共同建立了非整倍体如何通过对形态的基因剂量依赖性调节使 能够与其宿主可逆适应。
