C-di-GMP regulates Pseudomonas aeruginosa stress response to tellurite during both planktonic and biofilm modes of growth

Stress response plays an important role on microbial adaptation under hostile environmental conditions. It is generally unclear how the signaling transduction pathway mediates a stress response in planktonic and biofilm modes of microbial communities simultaneously. Here, we showed that metalloid tellurite (TeO₃^2-) exposure induced the intracellular content of the secondary messenger cyclic di-GMP (c-di-GMP) of Pseudomonas aeruginosa. Two diguanylate cyclases (DGCs), SadC and SiaD, were responsible for the increased intracellular content of c-di-GMP. Enhanced c-di-GMP levels by TeO₃^2- further increased P. aeruginosa biofilm formation and resistance to TeO₃^2-. P. aeruginosa "sadC "siaD and PAO1/p lac-yhjH mutants with low intracellular c-di-GMP content were more sensitive to TeO₃^2- exposure and had low relative fitness compared to the wild-type PAO1 planktonic and biofilm cultures exposed to TeO₃^2-. Our study provided evidence that c-di-GMP level can play an important role in mediating stress response in microbial communities during both planktonic and biofilm modes of growth.