Abstract
Infections with Pseudomonas aeruginosa increase morbidity in primary ciliary dyskinesia (PCD) and cystic fibrosis (CF) patients. Both diseases are associated with a defect of the mucociliary clearance; in PCD caused by non-functional cilia, in CF by changed mucus. Whole genome sequencing of P. aeruginosa isolates from CF patients has shown that persistence of clonal lineages in the airways is facilitated by genetic adaptation. It is unknown whether this also applies to P. aeruginosa airway infections in PCD. We compared within-host evolution of P. aeruginosa in PCD and CF patients. P. aeruginosa isolates from 12 PCD patients were whole genome sequenced and phenotypically characterised. Ten out of 12 PCD patients were infected with persisting clone types. We identified convergent evolution in eight genes, which are also important for persistent infections in CF airways: genes related to antibiotic resistance, quorum sensing, motility, type III secretion and mucoidity. We document phenotypic and genotypic parallelism in the evolution of P. aeruginosa across infected patients with different genetic disorders. The parallel changes and convergent adaptation and evolution may be caused by similar selective forces such as the intensive antibiotic treatment and the inflammatory response, which drive the evolutionary processes.
Highlights
Pseudomonas aeruginosa is an opportunistic pathogen that frequently causes chronic infections in the upper and lower airways of primary ciliary dyskinesia (PCD) and cystic fibrosis (CF) patients[1,2,3,4]
It has previously been documented that clone types can be transmitted between CF patients[17,29], and since the Copenhagen CF clinic and the Danish PCD Centre are located at close proximity in the hospital it may increase the risk of patients being exposed to the same P. aeruginosa clone types
The PCD patients investigated in this study have been infected with P. aeruginosa for varying lengths of time, but 10 out of 12 patients have an infection history more comparable to the recently described cohort of young CF patients[17] with persistent airway infections (Fig. 1) than to chronically infected older CF patients[12]
Summary
Pseudomonas aeruginosa is an opportunistic pathogen that frequently causes chronic infections in the upper and lower airways of primary ciliary dyskinesia (PCD) and cystic fibrosis (CF) patients[1,2,3,4]. The cilia drive the mucus and pathogens out of the airways where they are cleared by coughing, expectoration, or swallowing of sputum. We hypothesise that if the main selective pressures found in the PCD and CF airways are the host immune defence system and the frequent presence of antibiotics, the adaptation and evolution of P. aeruginosa should not differ significantly between the two groups of patients. Overproduction of alginate (mucoidity), slow growth, altered biofilm mode of growth, loss of motility, quorum sensing and protease production[10,13,18,19,20,21] These adaptational changes are to a large degree associated with antibiotic treatments, the activity of the immune defence, and specific physico/chemical characteristics of the CF mucus. Similar adaptive and evolutionary investigations have to our knowledge never been performed in P. aeruginosa from PCD patients
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