Culture and Adaptation of Pseudomonas aeruginosa During Early Infection in Children With Cystic Fibrosis

BACKGROUND: Relatively little is known about Pseudomonas aeruginosa lineages during early infection in individuals with cystic fibrosis (CF). The Early Pseudomonas Infection Control Clinical Trial (EPIC-CT), which treated individuals with CF and newly detected P. aeruginosa infections, presents an ideal opportunity to study this phenomenon. METHODS: We performed whole-genome sequencing on 572 P. aeruginosa isolates from 190 EPIC-CT subjects. RESULTS: We identified 203 P. aeruginosa lineages causing newly detected infections near the time of enrollment of these subjects. Twelve subjects were initially infected with more than one P. aeruginosa lineage, and 20 subjects had different PA lineages detected during the follow-up period of the EPIC-CT. Of the 203 lineages causing initial infections, 144 were not detected again by culture and 59 were detected again despite antibiotic therapy. Multilocus sequence typing was as accurate as whole genome single nucleotide variant (SNV) typing in discriminating lineages, but pulsed-field gel electrophoresis inaccurately classified 17 genetically related isolates as distinct. Although subjects were infected for a relatively short time, 23 P. aeruginosa genes acquired nonsynonymous SNVs in at least 2 subjects. Of these, 14 had been previously identified as pathoadaptive, confirming that such mutations can emerge early in CF infections. CONCLUSIONS: Our study demonstrates the complexity of early P. aeruginosa infections in people with CF and the potential of these complexities to confound interpretation of antibiotic efficacy studies.