The c-di-GMP phosphodiesterase PipA (PA0285) regulates auto-aggregation and Pf4 2 bacteriophage production in Pseudomonas aeruginosa PAO1

In Pseudomonas aeruginosa PAO1, 41 genes encode proteins predicted to be involved in the production or degradation of c-di-GMP, a ubiquitous secondary messenger that regulates a variety of physiological behaviours closely related to biofilm and aggregate formation. Despite the extensive effort, the whole picture of this important signalling network is still unclear with one third of these proteins remain uncharacterized. Here, we showed that the deletion of pipA, which produces a protein containing two PAS domains upstream of a GGDEF-EAL tandem, significantly increased the intracellular c-di-GMP level and promoted the formation of aggregates both on surfaces and in planktonic cultures. However, this regulatory effect was not contributed by the two classic pathways modulating biofilm formation, EPS overproduction or motility inhibition. Our work therefore for the first time showed that a c-di-GMP phosphodiesterase can regulate bacteriophage production and provided new insights on the relationship between bacteriophage and bacterial aggregation.