WS14.2 Surviving and thriving in the airway: how the arginine specific autotransporter aminopeptidase could promote the success of Pseudomonas aeruginosa in the CF lung

Abstract

(at both the individual and population level). Sputum samples from a cohort of G551D CF patients treated with ivacaftor were analysed to see if mutations such as those in LasR are still favorable in the P. aeruginosa population after the initiation of treatment with this drug. We hypothesised that the partial correction of the CF phenotype post-therapy would alter the milieu sufficiently, such that previouslyadaptive mutations would become maladaptive. Although there was a drop in bacterial density over time, P. aeruginosa was present both before and after initiation of ivacaftor. A culture-independent approach to quantify the frequency of mutations before and after initiation of ivacaftor assessed the following genes: lasI, lasR, rhlI, rhlR, qscR, pqsR, algU, rpoS, mucA, mutS, and mutL for changes in the population frequency of mutations. Some genes were selected against in ivacaftortreated patients, consistent with the idea that phenotypic correction of the CF lung milieu makes these mutations disadvantageous, and suggesting that selective targeting of the phenotypes might be beneficial to patients with CF who are not candidates for CFTR modulator therapy.