Abstract
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.
Highlights
Pseudomonas aeruginosa can cause opportunistic infections in humans, such as cystic fibrosis lung infections, burn wounds and urinary tract infections (Bodey et al, 1983)
We found that low intracellular c-di-GMP content induced expression of the QS systems, the rhl and pqs systems, which led to increased production of several virulence factors, such as rhamnolipids and pyocyanin
The late log phase P. aeruginosa plac-yhjH mutant cells contained reduced c-di-GMP content due to the constitutively expressed YhjH PDE protein (Gjermansen et al, 2010; Chua et al, 2013; Figure 1A), mimicking cells freshly dispersed from the biofilms
Summary
Pseudomonas aeruginosa can cause opportunistic infections in humans, such as cystic fibrosis lung infections, burn wounds and urinary tract infections (Bodey et al, 1983). This is attributed to its ability to form biofilms and produce an abundance of virulence factors to impair the host immune response (Bjarnsholt et al, 2009; Fazli et al, 2011). Low c-di-GMP Induces Quorum Sensing degraded by phosphodiesterases (PDEs) (Hengge, 2009). The wspR DGC is important in the sensing of reactive oxygen species (ROS) and formation of biofilms resilient to ROS stress (Chua et al, 2016a)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
