The ExoY phenotype of high-copy-number recombinants is not detectable in natural isolates.

The nucleotidyl cyclase ExoY is an effector protein of the type III secretion system of We compared the cyclic nucleotide production and lung disease phenotypes caused by the ExoY-overexpressing strain PA103Δ pUCP, its vector control strain PA103Δ pUCP18, its loss-of-function control PA103Δ pUCP K81M and natural ExoY-positive and ExoY-negative isolates in a murine acute airway infection model. Only the carrier of the plasmid produced high levels of cUMP and caused the most severe course of infection. The pathology ascribed to ExoY from studies using the high-copy-number plasmid on mammalian cells and was not observed with natural isolates. This indicates that the role of ExoY during infection with real-life still needs to be resolved.