Initial cyclic-di-GMP upregulation triggers sporadic cellular expansion leading to improved cellular survival

Bacterial second messenger c-di-GMP upregulation is associated with the transition from planktonic to sessile microbial lifestyle, inhibiting cellular motility, and virulence. However, in-depth elucidation of the cellular processes resulting from c-di-GMP upregulation has not been fully explored. Here, we report the role of upregulated cellular c-di-GMP in promoting planktonic cell growth of Escherichia coli K12 and Pseudomonas aeruginosa PAO1. We found a rapid expansion of cellular growth during initial cellular c-di-GMP upregulation, resulting in a larger planktonic bacterial population. The initial increase in c-di-GMP levels promotes bacterial swarming motility during the growth phase, which is subsequently inhibited by the continuous increase of c-di-GMP, and ultimately facilitates the formation of biofilms. We demonstrated that c-di-GMP upregulation triggers key bacterial genes linked to bacterial growth, swarming motility, and biofilm formation. These genes are mainly controlled by the master regulatory genes csgD and csrA . This study provides us a glimpse of the bacterial behavior of evading potential threats through adapting lifestyle changes via c-di-GMP regulation.