Rafael F Castelli, Alana Pereira, Leandro Honorato, Alessandro Valdez, Haroldo C de Oliveira, Jaqueline M Bazioli, Ane W A Garcia, Tabata D'Maiella Freitas Klimeck, Flavia C G Reis, Amanda C Camillo-Andrade, Marlon D M Santos, Paulo C Carvalho, Oscar Zaragoza, Charley C Staats, Leonardo Nimrichter, Taícia P Fill, Marcio L Rodrigues
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引用次数: 0
摘要
小分子是真菌胞外囊泡(EVs)的组成部分,但它们的生物学作用却只为人所知。NOP16 是一个真核基因,它是苯并咪唑类药物对抗德氏隐球菌活性的必需基因。在本研究中,在对预期缺乏 NOP16 表达的 C. deuterogattii 突变体进行表型鉴定时,我们观察到 EV 的产生减少。全基因组测序、RNA-Seq 和细胞蛋白质组学发现,与我们最初的发现相反,这些突变体表达了 Nop16,但可能参与糖运输的 14 个基因的表达发生了改变。基于这一观察结果,我们将这些突变株命名为 Past1 和 Past2,它们代表了可能发生改变的糖转运。对野生型细胞及Past1和Past2突变株产生的EVs的小分子组成进行分析后发现,不仅EVs数量减少,而且小分子组成也发生了改变。在Galleria mellonella感染模型中,Past1和Past2突变株具有低病毒性。当野生型细胞产生的EV而非突变型EV与G. mellonella中的突变型细胞共同注射时,低病毒性表型得以恢复。这些结果将EV的生物发生、货物和隐球菌的毒力联系起来。
Corrected and republished from: "Extracellular Vesicle Formation in Cryptococcus deuterogattii Impacts Fungal Virulence".
Small molecules are components of fungal extracellular vesicles (EVs), but their biological roles are only superficially known. NOP16 is a eukaryotic gene that is required for the activity of benzimidazoles against Cryptococcus deuterogattii. In this study, during the phenotypic characterization of C. deuterogattii mutants expected to lack NOP16 expression, we observed a reduced EV production. Whole-genome sequencing, RNA-Seq, and cellular proteomics revealed that, contrary to our initial findings, these mutants expressed Nop16 but exhibited altered expression of 14 genes potentially involved in sugar transport. Based on this observation, we designated these mutant strains as Past1 and Past2, representing potentially altered sugar transport. Analysis of the small molecule composition of EVs produced by wild-type cells and the Past1 and Past2 mutant strains revealed not only a reduced number of EVs but also an altered small molecule composition. In a Galleria mellonella model of infection, the Past1 and Past2 mutant strains were hypovirulent. The hypovirulent phenotype was reverted when EVs produced by wild-type cells, but not mutant EVs, were co-injected with the mutant cells in G. mellonella. These results connect EV biogenesis, cargo, and cryptococcal virulence.
期刊介绍:
Infection and Immunity (IAI) provides new insights into the interactions between bacterial, fungal and parasitic pathogens and their hosts. Specific areas of interest include mechanisms of molecular pathogenesis, virulence factors, cellular microbiology, experimental models of infection, host resistance or susceptibility, and the generation of innate and adaptive immune responses. IAI also welcomes studies of the microbiome relating to host-pathogen interactions.