Abstract
The cyclic di-GMP (c-di-GMP) second messenger represents a signaling system that regulates many bacterial behaviors and is of key importance for driving the lifestyle switch between motile loner cells and biofilm formers. This review provides an up-to-date summary of c-di-GMP pathways connected to biofilm formation by the opportunistic pathogen P. aeruginosa. Emphasis will be on the timing of c-di-GMP production over the course of biofilm formation, to highlight non-uniform and hierarchical increases in c-di-GMP levels, as well as biofilm growth conditions that do not conform with our current model of c-di-GMP.