Evolution and diversification of Pseudomonas aeruginosa in the paranasal sinuses of cystic fibrosis children have implications for chronic lung infection

Abstract

The opportunistic pathogen Pseudomonas aeruginosa is a frequent colonizer of the airways of patients suffering from cystic fibrosis (CF). Depending on early treatment regimens, the colonization will, with high probability, develop into chronic infections sooner or later, and it is important to establish under which conditions the switch to chronic infection takes place. In association with a recently established sinus surgery treatment program for CF patients at the Copenhagen CF Center, colonization of the paranasal sinuses with P. aeruginosa has been investigated, paralleled by sampling of sputum from the same patients. On the basis of genotyping and phenotypic characterization including transcription profiling, the diversity of the P. aeruginosa populations in the sinuses and the lower airways was investigated and compared. The observations made from several children show that the paranasal sinuses constitute an important niche for the colonizing bacteria in many patients. The paranasal sinuses often harbor distinct bacterial subpopulations, and in the early colonization phases there seems to be a migration from the sinuses to the lower airways, suggesting that independent adaptation and evolution take place in the sinuses. Importantly, before the onset of chronic lung infection, lineages with mutations conferring a large fitness benefit in CF airways such as mucA and lasR as well as small colony variants and antibiotic-resistant clones are part of the sinus populations. Thus, the paranasal sinuses potentially constitute a protected niche of adapted clones of P. aeruginosa, which can intermittently seed the lungs and pave the way for subsequent chronic lung infections.

Evolutionary remodeling of global regulatory networks during long-term bacterial adaptation to human hosts

“…1), which contrasts the frequent observations of phenotypic heterogeneity in clonal P. aeruginosa populations within the same CF respiratory specimen (22)(23)(24)(25)(26) and evolutionary theory predicting enhanced diversification and specializing adaptation in spatially structured environments (27,28). However, the evolution of the mucA DK2 algT…”

Pseudomonas aeruginosa In VitroPhenotypes Distinguish Cystic Fibrosis Infection Stages and Outcomes

“…Also, recent analyses showed that traditional culture methods (i.e., isolating a small number of morphologically different bacterial colonies from each culture) frequently underrepresent the P. aeruginosa diversity in individual samples of CF respiratory secretions during chronic infection with respect to several phenotypes (44)(45)(46)(47); therefore, even the large isolate collection in this study likely undersampled the phenotypic diversity of P. aeruginosa in each subject. Similarly, it is possible that sputum and OP specimens are not sufficiently sensitive to reflect the earliest stages of infection, whether of the lower or upper airways (48,49), potentially explaining the observed high frequency in our "early" isolates of phenotypes commonly associated with adaptation.…”

Sinus Bacteriology in Patients with Cystic Fibrosis or Primary Ciliary Dyskinesia: A Systematic Review

“…12 In the early stages of lung colonization, the migration of pathogens may mainly occur in a downward direction, with the sinuses as a primary focus. 12 Several studies found concordance between upper and lower airway bacteriology in both patients with CF [13][14][15][16][17] and those with PCD. 11 Although the pattern of bacterial flora in the lower airways has been extensively studied, the upper airways have drawn limited attention.…”