Selective Sweeps and Parallel Pathoadaptation Drive Pseudomonas aeruginosa Evolution in the Cystic Fibrosis Lung

摘要: ABSTRACT Pulmonary infections caused by Pseudomonas aeruginosa are a recalcitrant problem in cystic fibrosis (CF) patients. While the clinical implications and long-term evolutionary patterns of these well studied, we know little about short-term population dynamics that enable this pathogen to persist despite aggressive antimicrobial therapy. Here, describe genomic analysis 233 P. isolates collected from 12 sputum specimens obtained over 1-year period single patient. Whole-genome sequencing susceptibility profiling identified expansion two clonal lineages. The first lineage originated coalescence entire sample less than 3 years before end study gave rise high-diversity ancestral population. second occurred 2 years later derived with strong signal positive selection. These events show characteristics consistent recurrent selective sweeps. cannot identify specific mutations responsible for origins lineages, find majority occur loci previously associated virulence resistance. Additionally, approximately one-third all mutated multiple times, highlighting importance parallel pathoadaptation. One such locus is gene encoding penicillin-binding protein 3, which received three independent mutations. Our functional alleles shows they provide differential fitness benefits dependent on antibiotic under data reveal bacterial populations can undergo extensive dramatic changes not revealed lower-resolution analyses. IMPORTANCEPseudomonas opportunistic significant morbidity mortality Once it has colonized lung CF, highly resilient rarely eradicated. This presents deep sampling examination fine-scale lungs chronically infected CF We diversity driven emergence within patient potential adaptive variants events. high-resolution strategy thus reveals important intraspecies explain clinically phenomenon evident at community structure.