Chronic biofilm infections are caused by a set of pathogens commonly referred to as ESKAPE pathogens, which includes Pseudomonas aeruginosa. These pathogens share their ability to form biofilms on medical device surfaces and resist antibiotic therapy. Cyclic-di-GMP is a signaling nucleotide that often promotes biofilm formation in bacteria. Cyclic-di-GMP is maintained in a steady state level by biosynthesis by diguanylate cyclases and linearization into pGpG by phoshpodiesterases. pGpG was recycled into GMP by an unknown enzyme. In this talk, I will discuss our work on understanding the signaling of c-di-GMP through identification of c-di-GMP receptor proteins, how pGpG is specifically degraded by oligoribonuclease (Orn), the structural characteristics of Orn, the basis for Orn essentiality, and how linear dinucleotides can serve as a quality control mechanism in prokaryotic cells. The talk will conclude on recent studies on the ability of P. aeruginosa to cause disease in an animal model of catheter-associated urinary tract infection.