carP, encoding a Ca2+-regulated putative phytase, is evolutionarily conserved in Pseudomonas aeruginosa and has potential as a biomarker

Abstract

Pseudomonas aeruginosa infects patients with cystic fibrosis, burns, wounds and implants. Previously, our group showed that elevated Ca2+ positively regulates the production of several virulence factors in P. aeruginosa , such as biofilm formation, production of pyocyanin and secreted proteases. We have identified a Ca2+-regulated β-propeller putative phytase, CarP, which is required for Ca2+ tolerance, regulation of the intracellular Ca2+ levels, and plays a role in Ca2+ regulation of P. aeruginosa virulence. Here, we studied the conservation of carP sequence and its occurrence in diverse phylogenetic groups of bacteria. In silico analysis revealed that carP and its two paralogues PA2017 and PA0319 are primarily present in P. aeruginosa and belong to the core genome of the species. We identified 155 single nucleotide alterations within carP, 42 of which lead to missense mutations with only three that affected the predicted 3D structure of the protein. PCR analyses with carP-specific primers detected P. aeruginosa specifically in 70 clinical and environmental samples. Sequence comparison demonstrated that carP is overall highly conserved in P. aeruginosa isolated from diverse environments. Such evolutionary preservation of carP illustrates its importance for P. aeruginosa adaptations to diverse environments and demonstrates its potential as a biomarker.

Calcium-Regulated Protein CarP Responds to Multiple Host Signals and Mediates Regulation of Pseudomonas aeruginosa Virulence by Calcium

“…Uncovering novel components of the Ca 21 regulatory network will likely reveal previously uncharacterized factors controlling and defining the ability of human pathogens to invade, persist, and cause diseases. Previously, we identified one such component, a putative b-propeller phytase, CarP, encoded within the core genome of P. aeruginosa (73), that plays an important role in maintaining Ca 21 in homeostasis and that is required for cell tolerance to elevated Ca 21 and Ca 21 regulation of pyocyanin production and swarming (48). Here, we show that in addition to the role of carP in P. aeruginosa virulence, its transcription is regulated by multiple host and bacterial regulatory factors (Fig.…”