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转录组分析揭示了 Gln3 在氨基酸吸收和氟康唑耐药中的作用。

Transcriptome Analysis Unveils Gln3 Role in Amino Acids Assimilation and Fluconazole Resistance in .

机构信息

Unidad de Genómica Avanzada, Laboratorio Nacional de Genómica para la Biodiversidad (Langebio), CINVESTAV, Mexico.

División de Biología Molecular, Instituto Potosino de Investigación Científica y Tecnológica A. C. (IPICYT), Mexico.

出版信息

J Microbiol Biotechnol. 2021 May 28;31(5):659-666. doi: 10.4014/jmb.2012.12034.

DOI:10.4014/jmb.2012.12034
PMID:33879640
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9705932/
Abstract

After , is one of the most common fungal species associated with candidemia in nosocomial infections. Rapid acquisition of nutrients from the host is important for the survival of pathogens which possess the metabolic flexibility to assimilate different carbon and nitrogen compounds. In , nitrogen assimilation is controlled through a mechanism known as Nitrogen Catabolite Repression (NCR). NCR is coordinated by the action of four GATA factors; two positive regulators, Gat1 and Gln3, and two negative regulators, Gzf3 and Dal80. A mechanism in similar to NCR in has not been broadly studied. We previously showed that in , Gln3, and not Gat1, has a major role in nitrogen assimilation as opposed to what has been observed in in which both factors regulate NCR-sensitive genes. Here, we expand the knowledge about the role of Gln3 from through the transcriptional analysis of BG14 and strains. Approximately, 53.5% of the detected genes were differentially expressed (DEG). From these DEG, amino acid metabolism and ABC transporters were two of the most enriched KEGG categories in our analysis (Up-DEG and Down-DEG, respectively). Furthermore, a positive role of Gln3 in AAA assimilation was described, as was its role in the transcriptional regulation of . Finally, an unexpected negative role of Gln3 in the gene regulation of ABC transporters and and its associated transcriptional regulator was found. This observation was confirmed by a decreased susceptibility of the strain to fluconazole.

摘要

在医学领域中,最常见的真菌物种之一是念珠菌,它与医院获得性感染中的念珠菌血症有关。病原体从宿主中快速获取营养对于它们的生存至关重要,因为它们具有代谢灵活性,可以同化不同的碳和氮化合物。在中,氮同化受到一种称为氮分解代谢阻遏(NCR)的机制控制。NCR 由四个 GATA 因子的作用协调;两个正调节剂 Gat1 和 Gln3,以及两个负调节剂 Gzf3 和 Dal80。中类似于 NCR 的机制尚未得到广泛研究。我们之前曾表明,在中,Gln3 而不是 Gat1 在氮同化中起主要作用,而在中观察到的情况则相反,在中,这两个因素都调节 NCR 敏感基因。在这里,我们通过对 BG14 和 菌株的转录分析扩展了对 Gln3 在 中的作用的认识。大约有 53.5%的检测基因表达差异(DEG)。在这些 DEG 中,氨基酸代谢和 ABC 转运蛋白是我们分析中最丰富的两个 KEGG 类别(上调 DEG 和下调 DEG)。此外,描述了 Gln3 在 AAA 同化中的积极作用,以及它在基因转录调控中的作用。最后,发现了 Gln3 在 ABC 转运蛋白 和 及其相关转录调节剂 的基因调控中的意外负作用。这一观察结果通过 菌株对氟康唑的敏感性降低得到了证实。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9111/9705932/7827e76a3db9/jmb-31-5-659-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9111/9705932/2fbf0a111eff/jmb-31-5-659-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9111/9705932/f18d9e6db516/jmb-31-5-659-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9111/9705932/7cc69bbb81ee/jmb-31-5-659-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9111/9705932/7827e76a3db9/jmb-31-5-659-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9111/9705932/2fbf0a111eff/jmb-31-5-659-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9111/9705932/f18d9e6db516/jmb-31-5-659-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9111/9705932/7cc69bbb81ee/jmb-31-5-659-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9111/9705932/7827e76a3db9/jmb-31-5-659-f4.jpg

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