Pérez-Delos Santos Francisco J, Riego-Ruiz Lina
Laboratory of Functional and Comparative Genomics, División de Biología Molecular, Instituto Potosino de Investigación Científica y Tecnológica (IPICYT), A. C., San Luis Potosí, México.
Microbiology (Reading). 2016 Aug;162(8):1490-1499. doi: 10.1099/mic.0.000312. Epub 2016 May 24.
After Candida albicans, the yeast Candida glabrata ranks second as an aetiological agent of candidaemia and is the most frequently encountered non-Candida albicans species in patients with invasive candidiasis. Transcriptome analysis in C. albicans, C. glabrata and Cryptoccocus neoformans has revealed that, when engulfed by macrophages, these yeasts upregulate genes involved in nutrient acquisition, including nitrogen transporters such as the general amino acid permease Gap1, the dicarboxylic amino acid permease Dip5, the basic amino acid permease Can1 and the ammonium permeases Mep1 and Mep2. Nitrogen assimilation has been well studied in model species of fungi, such as Aspergillus nidulans, Neurospora crassa and Saccharomyces cerevisiae. However, little is known about nitrogen assimilation in C. glabrata. In the present study, we report a major role for Gln3 in the assimilation of glutamine, ammonium and proline. Ure2 also has a role in nitrogen assimilation, but it is only observable in ammonium and glutamine. In addition, Gat1 has a minor role, which is only observable in the absence of Ure2 and Gln3. Gln3 is absolutely necessary for full ammonium uptake from media. We have also shown that MEP2 gene expression in C. glabrata is completely dependent on Gln3, whereas GAP1 regulation is mainly exerted by Gln3, with the exception of proline where Gat1 has a minor role. In addition, in C. glabrata Ure2 appears to be a negative regulator of these NCR-sensitive genes, similarly to what has been described in S. cerevisiae. Our data place Gln3 as a key regulator of nitrogen assimilation.
在白色念珠菌之后，光滑念珠菌作为念珠菌血症的病原体位列第二，并且是侵袭性念珠菌病患者中最常遇到的非白色念珠菌物种。对白色念珠菌、光滑念珠菌和新型隐球菌的转录组分析表明，当被巨噬细胞吞噬时，这些酵母会上调参与营养获取的基因，包括氮转运蛋白，如通用氨基酸通透酶Gap1、二羧酸氨基酸通透酶Dip5、碱性氨基酸通透酶Can1以及铵通透酶Mep1和Mep2。氮同化在丝状真菌的模式物种中，如构巢曲霉、粗糙脉孢菌和酿酒酵母中已有深入研究。然而，关于光滑念珠菌中的氮同化知之甚少。在本研究中，我们报道了Gln3在谷氨酰胺、铵和脯氨酸同化中的主要作用。Ure2在氮同化中也有作用，但仅在铵和谷氨酰胺中可观察到。此外，Gat1起次要作用，仅在缺乏Ure2和Gln3时可观察到。Gln3对于从培养基中充分摄取铵是绝对必要的。我们还表明，光滑念珠菌中MEP2基因的表达完全依赖于Gln3，而GAP1的调控主要由Gln3发挥，脯氨酸除外，此时Gat1起次要作用。此外，在光滑念珠菌中，Ure2似乎是这些NCR敏感基因的负调节因子，这与酿酒酵母中所描述的情况类似。我们的数据表明Gln3是氮同化的关键调节因子。
