Tracking eco-evolutionary patterns among oropharyngeal pathobiome members in a pediatric cystic fibrosis cohort

Polymicrobial airway colonization is common in individuals with cystic fibrosis (CF). Pathogen communities typically follow an ecological succession in which early colonizers, such as Haemophilus influenzae and Staphylococcus aureus, are later joined by Pseudomonas aeruginosa. Although adaptation to the lung environment is well described for single pathogens in adult people with CF, much less is known about the role of pathogen interactions and how changes in individual pathogens influence community dynamics at the early stages of disease. To address these questions, we combined genome sequencing with phenotypic screens and pathogen interaction assays using longitudinal clinical isolates (19 P. aeruginosa, 44 S. aureus, and 21 H. influenzae) collected from 23 children with CF (0-7.9 years of age) enrolled in the Swiss Cystic Fibrosis Infant Lung Development (SCILD) cohort. Our analysis suggests that early pathogen communities are characterized by a combination of strain turnover and persistence of specific isolates that go along with cohort-wide, age-associated shifts in pathogen phenotypes and interaction patterns. Most notably, quorum-sensing-deficient P. aeruginosa variants repeatedly emerged, showing reduced protease production and diminished inhibition of S. aureus and H. influenzae. These changes demonstrate that P. aeruginosa isolates from older children exhibit reduced antagonism toward co-occurring pathogens via secreted factors. Together, our results show that ecological and evolutionary dynamics between pathobiome members may play an underappreciated role in shaping CF lung disease during early childhood.

Our study shows how bacterial communities in the lungs of children with cystic fibrosis change during the earliest stages of disease. By tracking three major pathogens over time, we found that both replacement of strains and persistence shape colonization dynamics and pathogen interaction patterns. In particular, Pseudomonas aeruginosa frequently showed mutations that reduced its production of harmful compounds and weakened its ability to inhibit other bacteria. These changes indicate that interspecies interactions are dynamic during early childhood. Understanding these early interaction patterns provides useful cues about potential future microbial management in cystic fibrosis.