Abstract
Pseudomonas aeruginosa is the archetypal cystic fibrosis (CF) pathogen. However, the clinical course experienced by infected individuals varies markedly. Understanding these differences is imperative if further improvements in outcomes are to be achieved. Multiple studies have found that patients infected with epidemic P. aeruginosa (ePA) strains may have a worse clinical prognosis than those infected with unique, non-clonal strains. Additionally, the traditionally uncultured CF lung bacterial community (i.e., CF microbiome) may further influence the outcome. We sought to identify if these two important variables, not identified through routine culture, associate and together may contribute to disease pathogenesis. Patients were classified as being infected with Prairie Epidemic ePA (PES) or a non-clonal strain, unique PA strains (uPA), through a retrospective assessment of a comprehensive strain biobank using a combination of PFGE and PES-specific PCR. Patients were matched to age, sex, time-period controls and sputum samples from equivalent time periods were identified from a sputum biobank. Bacterial 16S rRNA gene profiling and Pseudomonas qPCR was used to characterize the respiratory microbiome. We identified 31 patients infected with PES and matched them with uPA controls. Patients infected with PES at baseline have lower microbial diversity (P = 0.02) and higher P. aeruginosa relative abundance (P < 0.005). Microbial community structure was found to cluster by PA strain type, although it was not the main determinant of community structure as additional factors were also found to be drivers of CF community structure. Communities from PES infected individuals were enriched with Pseudomonas, Streptococcus and Prevotella OTUs. The disproportionate disease experienced by ePA infected CF patients may be mediated through a combination of pathogen-pathogen factors as opposed to strictly enhanced virulence of infecting P. aeruginosa strains.
Highlights
Cystic fibrosis (CF) lung disease is characterized by thickened secretions that impair mucociliary function, thereby reducing the clearance of inhaled material (Gibson et al, 2003)
The control cohort consisted of 31 unique PA strains (uPA) infected patients (13 male; 18 female) and excluded patients infected with any other epidemic strain
In a longitudinal study of CF adults, patients with chronic Prairie Epidemic Strain (PES) infection had a 4.16 greater hazard ratio for progression to death/lung transplantation compared to those without P. aeruginosa, and 1.77 greater hazard ratio to those infected with unique P. aeruginosa strains (Somayaji et al, 2017)
Summary
Cystic fibrosis (CF) lung disease is characterized by thickened secretions that impair mucociliary function, thereby reducing the clearance of inhaled material (Gibson et al, 2003). P. aeruginosa virulence and its conversion to a hyperalginate producing mucoid phenotype during chronic infections is further associated with progressive decline in lung function, increased risk of hospitalization and reduced survival (Henry et al, 1992; Emerson et al, 2002; Li et al, 2005). Our research group identified a novel strain of P. aeruginosa, termed the Prairie Epidemic Strain (PES), infecting CF patients attending the Calgary Adult CF Clinic (CACFC) (Parkins et al, 2014). PES was found to represent ∼30% of chronically P. aeruginosa infected CF adult patients within the clinic and was identified infecting patients newly transitioning from neighboring Prairie-based Canadian CF centers over 25 years, suggesting broad endemicity (Somayaji et al, 2017; Middleton et al, 2018)
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