Challenges in using transcriptome data to study the c-di-GMP signaling network in Pseudomonas aeruginosa clinical isolates.

Melisa Gür, Jelena Erdmann, Anke Will, Ziwei Liang, Jens Bo Andersen, Tim Tolker-Nielsen, Susanne Häussler
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引用次数: 0

Abstract

In the Pseudomonas aeruginosa type strain PA14, 40 genes are known to encode for diguanylate cyclases (DGCs) and/or phosphodiesterases (PDEs), which modulate the intracellular pool of the nucleotide second messenger c-di-GMP. While in general, high levels of c-di-GMP drive the switch from highly motile phenotypes towards a sessile lifestyle, the different c-di-GMP modulating enzymes are responsible for smaller and in parts nonoverlapping phenotypes. In this study, we sought to utilize previously recorded P. aeruginosa gene expression datasets on 414 clinical isolates to uncover transcriptional changes as a result of a high expression of genes encoding DGCs. This approach might provide a unique opportunity to bypass the problem that for many c-di-GMP modulating enzymes it is not known under which conditions their expression is activated. However, while we demonstrate that the selection of subgroups of clinical isolates with high versus low expression of sigma factor encoding genes served the identification of their downstream regulons, we were unable to confirm the predicted DGC regulons, because the high c-di-GMP associated phenotypes were rapidly lost in the clinical isolates,. Further studies are needed to determine the specific mechanisms underlying the loss of cyclase activity upon prolonged cultivation of clinical P. aeruginosa isolates.

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利用转录组数据研究铜绿假单胞菌临床分离株c-di-GMP信号网络的挑战。
在铜绿假单胞菌型菌株PA14中,已知有40个基因编码二胍酸环化酶(DGCs)和/或磷酸二酯酶(PDEs),它们调节核苷酸第二信使c-di-GMP的细胞内池。虽然一般来说,高水平的c-二gmp驱动高运动表型向固定生活方式的转变,但不同的c-二gmp调节酶负责较小的和部分不重叠的表型。在这项研究中,我们试图利用先前记录的414个临床分离株的铜绿假单胞菌基因表达数据集来揭示编码DGCs的基因高表达导致的转录变化。这种方法可能提供了一个独特的机会来绕过许多c-二gmp调节酶的问题,即不知道在什么条件下它们的表达被激活。然而,虽然我们证明了临床分离株中sigma因子编码基因高表达和低表达亚群的选择有助于鉴定其下游调控,但我们无法确认预测的DGC调控,因为高c-di-GMP相关表型在临床分离株中迅速丢失。需要进一步的研究来确定长期培养临床铜绿假单胞菌分离株后环化酶活性丧失的具体机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
3.30
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15 weeks
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