The transcriptional stress response of Candida albicans to weak organic acids.

The transcriptional stress response of Candida albicans to weak organic acids.
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DOI:
10.1534/g3.114.015941
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发表时间:
2015-01-29
期刊:
G3 (Bethesda, Md.)
影响因子:
--
通讯作者:
Pavelka N
Pavelka N
中科院分区:
其他
文献类型:
--
作者:
Cottier F;Tan AS;Chen J;Lum J;Zolezzi F;Poidinger M;Pavelka N

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白色念珠菌是人类最重要的真菌病原体,引起严重感染,特别是在医院和免疫功能低下的环境中。然而,它也是正常人类微生物组中最普遍的真菌,在那里它与数百万亿其他微生物细胞共享其栖息地。尽管弱有机酸(WOAs)是细菌微生物群产生的最丰富的代谢产物之一,但对其对C.白色念珠菌。在这里,我们使用了基于测序的分析策略,系统地研究了C。在处理后的几个时间点,白色念珠菌转化为乳酸、乙酸、丙酸和丁酸。我们的数据揭示了一个复杂的转录反应,与个人WOA触发独特的基因表达谱和急性和慢性暴露之间的重要差异。尽管有这些不同之处,我们发现每个WOA诱导的基因表达变化之间存在显著的重叠,这使我们发现了一个与其他先前发表的C.转录应激反应。通常由WOA上调的基因在几种铁转运蛋白中富集,这与细胞内铁浓度的总体降低有关。此外,长期暴露于任何WOA都会导致RNA合成和核糖体生物发生基因的下调,从而导致总RNA水平显着降低,特别是核糖体RNA水平显着降低。总之,这项研究表明,胃肠道菌群可能直接影响C。白念珠菌生理学通过生产WOA,与这种真菌如何与其宿主在健康和疾病相互作用的可能影响。
Candida albicans is the most important fungal pathogen of humans, causing severe infections, especially in nosocomial and immunocompromised settings. However, it is also the most prevalent fungus of the normal human microbiome, where it shares its habitat with hundreds of trillions of other microbial cells. Despite weak organic acids (WOAs) being among the most abundant metabolites produced by bacterial microbiota, little is known about their effect on C. albicans. Here we used a sequencing-based profiling strategy to systematically investigate the transcriptional stress response of C. albicans to lactic, acetic, propionic, and butyric acid at several time points after treatment. Our data reveal a complex transcriptional response, with individual WOAs triggering unique gene expression profiles and with important differences between acute and chronic exposure. Despite these dissimilarities, we found significant overlaps between the gene expression changes induced by each WOA, which led us to uncover a core transcriptional response that was largely unrelated to other previously published C. albicans transcriptional stress responses. Genes commonly up-regulated by WOAs were enriched in several iron transporters, which was associated with an overall decrease in intracellular iron concentrations. Moreover, chronic exposure to any WOA lead to down-regulation of RNA synthesis and ribosome biogenesis genes, which resulted in significant reduction of total RNA levels and of ribosomal RNA in particular. In conclusion, this study suggests that gastrointestinal microbiota might directly influence C. albicans physiology via production of WOAs, with possible implications of how this fungus interacts with its host in both health and disease.
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