Reduced Intracellular c-di-GMP Content Increases Expression of Quorum Sensing-Regulated Genes in Pseudomonas aeruginosa

Frontiers in Cellular and Infection Microbiology

Tolker-Nielsen, Tim¹  Jun Ting, Hui²  Suwanchaikasem, Pipob²  Lin Chua, Song²  Kau Kit Goh, Kelvin²  Pin Ng, Sean²  Li, Yingying³  Givskov, Michael³  Kohli, Gurjeet S.⁴  Cai, Zhao⁴  Liu, Yang⁴  Yang, Liang⁴ 

[1] Department of Immunology and Microbiology, Costerton Biofilm Center, University of Copenhagen, Denmark;Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore;School of Biological Sciences, Nanyang Technological University, Singapore;Singapore Centre for Environmental Life Sciences Engineering, Nanyang Technological University, Singapore

关键词: Pseudomonas aeruginosa;    cyclic-di-GMP;    Quorum Sensing;    PQS;    rhamnolipids;   

DOI  :  10.3389/fcimb.2017.00451

学科分类：生物科学（综合）

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

CC BY