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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 (TeO 3  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 TeO 3  2–  further increased  P. aeruginosa  biofilm formation and resistance to TeO 3  2– .  P. aeruginosa  Δ sadC Δ siaD  and PAO1/p  lac  - yhjH  mutants with low intracellular c-di-GMP content were more sensitive to TeO 3  2–  exposure and had low relative fitness compared to the wild-type PAO1 planktonic and biofilm cultures exposed to TeO 3  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.

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