Multiple diguanylate cyclase‐coordinated regulation of pyoverdine synthesis in Pseudomonas aeruginosa

Abstract

The nucleotide signalling molecule bis-(3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP) plays an essential role in regulating microbial virulence and biofilm formation. C-di-GMP is synthesized by diguanylate cyclase (DGC) enzymes and degraded by phosphodiesterase (PDE) enzymes. One intrinsic feature of c-di-GMP signalling is the abundance of DGCs and PDEs encoded by many bacterial species. It is unclear whether the different DGCs or PDEs coordinately establish the c-di-GMP regulation or function independently of each other. Here, we provide evidence that multiple DGCs are involved in regulation of c-di-GMP on synthesis of the major iron siderophore pyoverdine in Pseudomonas aeruginosa. Constitutive expression of the WspG or YedQ DGC in P. aeruginosa is able to induce its pyoverdine synthesis. Induction of pyoverdine synthesis by high intracellular c-di-GMP depends on the synthesis of exopolysaccharides and another two DGCs, SiaD and SadC. SiaD was found to boost the c-di-GMP synthesis together with constitutively expressing YedQ. The exopolysaccharides and the SiaD DGC were found to modulate the expression of the RsmY/RsmZ ncRNAs. Induction of the RsmY/RsmZ ncRNAs might enhance the pyoverdine synthesis through SadC. Our study sheds light on a novel multiple DGC-coordinated c-di-GMP regulatory mechanism of bacteria.

Efficacy of levofloxacin against biofilms of Pseudomonas aeruginosa isolated from patients with respiratory tract infections in vitro

“…Pseudomonas aeruginosa biofilms showed significant changes in their transcriptomic profiles after OFLX treatment compared to the untreated cells, with a total of 129 DEGs. Contrary to our expectations, there were only a few of these DEGs that were associated with the well‐known biofilm formation‐related genes like the quorum sensing genes ( lasI/R , rlhI/R , pqsR et c.) (Lee & Zhang, ) and cyclic diguanylate cyclase expression‐associated genes ( siaA and siaD ) (Chen et al., ). Instead, most of the DEGs did not have any specific function.…”

Reactive oxygen species drive evolution of pro-biofilm variants in pathogens by modulating cyclic-di-GMP levels

“…We also used ‘locked’ high and low c-di-GMP content strains of PAO1 by using the p lac -yedQ and p lac -yhjH plasmids, respectively. The yedQ gene encodes an E. coli DGC that synthesizes c-di-GMP [50,55,56], thus the exogenous addition of the p lac -yedQ would enable the constitutive production of c-di-GMP within the species, resulting in the highly aggregative nature of the colonies (electronic supplementary material, figure S1). The yhjH gene encodes an E. coli PDE that degrades c-di-GMP [56,57], so the presence of p lac -yhjH plasmid would cause the reduction of intracellular c-di-GMP levels.…”

An overview of siderophore biosynthesis among fluorescent Pseudomonads and new insights into their complex cellular organization

“…aeruginosa PAO1 cells. However, the molecular mechanisms have not yet been clearly elucidated (Delic‐Attree et al ., ; Zaborin et al ., ; Imperi et al ., ; Balasubramanian et al ., ; Chen et al ., ). Under strong iron‐restricted conditions, PVDI production can reach concentrations of approximately 80 μM for a culture of P .…”