Calcium signaling in Pseudomonas aeruginosa

P. aeruginosa is an opportunistic pathogen and a major cause of hospital acquired infections and severe chronic infections in endocarditis and cystic fibrosis (CF) patients. During such infections, it encounters elevated levels of Ca2+. Ca2+ regulates gene expression, physiology, and production of several virulence factors, thereby, enhancing adaptability and virulence of P. aeruginosa. This indicates signaling role of Ca2+ in P. aeruginosa, however, molecular mechanisms involved in Ca2+ regulation are yet unknown. In eukaryotes, Ca2+ is a well established intracellular signal regulating essential cellular processes. We aim to characterize the molecular mechanisms involved in Ca2+ regulation and ultimately test the intracellular signaling role of Ca2+ in P. aeruginosa. Our studies established that P. aeruginosa maintains submicromolar level of intracellular Ca2+ ([Ca2+]in), which transiently increases in response to external Ca2+ . We determined that Ca2+ homeostasis is maintained by multiple transporters and putative Ca2+ binding proteins, and that P. aeruginosa responds to Ca2+ by using a two-component regulatory system CarSR, which regulates the expression of genes encoding putative Ca2+ binding proteins. These proteins contribute to the maintenance of intracellular Ca2+ homeostasis, which, in turn, plays an important role in Ca2+ regulation of physiology and virulence. Finally, we showed that Ca2+ regulates quorum sensing (QS) signaling in P. aeruginosa by affecting the transcription of QS regulatory genes. The ongoing work using Ca2+ transient defective mutant is aiming to provide direct experimental evidence for role of Ca2+ as a secondary messenger