Reduced Intracellular c-di-GMP Content Increases Expression of Quorum Sensing-Regulated Genes in Pseudomonas aeruginosa.
Reduced Intracellular c-di-GMP Content Increases Expression of Quorum Sensing-Regulated Genes in Pseudomonas aeruginosa.
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DOI：
10.3389/fcimb.2017.00451
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发表时间：
2017
影响因子：
5.7
通讯作者：
Givskov M
中科院分区：
文献类型：
--
作者：
Lin Chua S;Liu Y;Li Y;Jun Ting H;Kohli GS;Cai Z;Suwanchaikasem P;Kau Kit Goh K;Pin Ng S;Tolker-Nielsen T;Yang L;Givskov M
Cyclic-di-GMP（c-di-GMP）是一种细胞内的第二信使，在许多细菌物种中控制生物膜的生命周期。高细胞内c-di-GMP含量通过减少生物膜基质的运动性和产生来增强生物膜形成，而生物膜细胞中的低c-di-GMP含量导致运动性和生物膜分散增加。虽然高c-di-GMP水平对细菌生活方式的影响已得到充分研究，但低c-di-GMP水平下细胞的生理学仍不清楚。在这里，我们发现，铜绿假单胞菌细胞具有高和低的细胞内c-di-GMP含量具有不同的转录组谱。与高c-di-GMP细胞相比，低c-di-GMP细胞中有535个基因上调，432个基因下调。有趣的是，与具有较高c-di-GMP含量的细胞相比，rhl和pqs群体感应（QS）操纵子在具有低细胞内c-di-GMP含量的细胞中以较高水平表达。pqs和rhl QS的诱导表达需要功能性PqsR，即pqs QS的转录调节因子。接下来，我们观察到在具有低c-di-GMP水平的铜绿假单胞菌细胞中pqs和rhl调节的毒力因子（如绿脓菌素和鼠李糖脂）的产生增加，赋予它们增加的细胞内存活率和对鼠巨噬细胞的细胞毒性。因此，我们的数据表明，低细胞内c-di-GMP水平的细菌可以诱导QS调节的毒力，特别是鼠李糖脂，削弱先天免疫系统的细胞成分。
Cyclic-di-GMP (c-di-GMP) is an intracellular secondary messenger which controls the biofilm life cycle in many bacterial species. High intracellular c-di-GMP content enhances biofilm formation via the reduction of motility and production of biofilm matrix, while low c-di-GMP content in biofilm cells leads to increased motility and biofilm dispersal. While the effect of high c-di-GMP levels on bacterial lifestyles is well studied, the physiology of cells at low c-di-GMP levels remains unclear. Here, we showed that Pseudomonas aeruginosa cells with high and low intracellular c-di-GMP contents possessed distinct transcriptome profiles. There were 535 genes being upregulated and 432 genes downregulated in cells with low c-di-GMP, as compared to cells with high c-di-GMP. Interestingly, both rhl and pqs quorum-sensing (QS) operons were expressed at higher levels in cells with low intracellular c-di-GMP content compared with cells with higher c-di-GMP content. The induced expression of pqs and rhl QS required a functional PqsR, the transcriptional regulator of pqs QS. Next, we observed increased production of pqs and rhl-regulated virulence factors, such as pyocyanin and rhamnolipids, in P. aeruginosa cells with low c-di-GMP levels, conferring them with increased intracellular survival rates and cytotoxicity against murine macrophages. Hence, our data suggested that low intracellular c-di-GMP levels in bacteria could induce QS-regulated virulence, in particular rhamnolipids that cripple the cellular components of the innate immune system.
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影响因子：
5.8
作者：
Chua SL;Ding Y;Liu Y;Cai Z;Zhou J;Swarup S;Drautz-Moses DI;Schuster SC;Kjelleberg S;Givskov M;Yang L
通讯作者：
Yang L
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
--
作者：
Diggle, Stephen P.;Matthijs, Sandra;Williams, Paul
通讯作者：
Williams, Paul
影响因子：
4
作者：
Bhattacharjee, Arunima;Nusca, Tyler D.;Hochbaum, Allon I.
通讯作者：
Hochbaum, Allon I.
影响因子：
3.6
作者：
Hisert, KB;MacCoss, M;Nathan, C
通讯作者：
Nathan, C