FEATURED NEW INVESTIGATOR Evolution of Pseudomonas aeruginosa type III secretion in cystic fibrosis: a paradigm of chronic infection

Pseudomonas aeruginosa (PA) from acute and chronic (eg, cysticfibrosis [CF]) infections differ in several respects, butthey can worsenprognosisin eachcontext. Factors that facilitate conversion from an acute to chronic phenotype are poorly understood. T3 secretion proteins are virulence factors associated with poorer outcomes in acute infections,but littleisknownabouttheirroleinCF.WewishedtocharacterizeT3secretioninCFPAisolatesandtoexamineitsroleinclinicaloutcomes.Atotalof114CFsubjectsweredividedinto3cohorts:1stinfectedindividuals,CIchildren,andadults.Serial respiratorycultureswereanalyzedforT3secretion.Serialspirometryandexacerbation data were collected prospectively. In 1st infection, 45.2% 6 9.1% of PA isolates secreted T3 proteins compared with 29.1% 6 4.2% and 11.5% 6 3.0% in CI children and CI adults, respectively (P , 0.001). An inverse correlation was observed between duration of PA infection and percent T3 positive isolates (r 5 ‐0.32, P , 0.001). Overall, no association was observed between T3 secretion and pulmonary outcomes, but in the subgroup of subjects who had at least 1 T3 positive organism, T3 secretion was inverselycorrelatedwiththeforcedexpiratoryvolumein1s(FEV1)decline(r 5‐0.35,P 5 0.02). In 1st infection, 82% of cultures grew either all or no T3-positive organisms. In these patients, T3 secretion was associated with a greater risk of subsequent PA isolation (P ,0.001).InCF, PAT3secretion decreaseswith residence time inlung,maypredict FEV1 decline in patients who have detectable T3 organisms, and may facilitate persistence after 1st infection. (Translational Research 2008;152:257‐264)