Adaptation of Pseudomonas aeruginosa to the cystic fibrosis lung and the role of shear stress in disrupting alginate matrix biofilms

Pseudomonas aeruginosa is a Gram-negative gamma-proteobacterium that can be found in a wide range of environments including water, soil, animals, and humans. However, due to its metabolic versatility and large genome encoding multiple virulence factors, this opportunistic pathogen is able to infect patients with severe wounds, immunocompromised individuals, and most importantly cystic fibrosis (CF) patients. In the first part of this thesis, we have typed 54 P. aeruginosa CF isolates using a novel genotyping approach based on the combination of Rep-PCR and multiplex PCR targeting ferripyoverdine siderophore receptor and pyocin genes. In the second part of the thesis we have studied the effect of shear stress on the transmissible P. aeruginosa isolate CF_PA39 grown in artificial sputum medium (ASM) at the transcriptomic (via RNA sequencing) and phenotypic level. In the third part of this thesis, we have determined the expression of marker genes associated with either the planktonic or biofilm lifestyle of P. aeruginosa, discovered in the course of this work, in sputum samples from CF patients receiving intrapulmonary percussive ventilation (IPV) at low or high frequency versus standard therapy.