PT - JOURNAL ARTICLE AU - Catherine R. Armbruster AU - Christopher W. Marshall AU - Jeffrey A. Melvin AU - Anna C. Zemke AU - Arkadiy I. Garber AU - John Moore AU - Kelvin Li AU - Paula F. Zamora AU - Ian L. Fritz AU - Christopher Manko AU - Madison Weaver AU - Jordan Gaston AU - Alison Morris AU - Barbara Methé AU - Stella E. Lee AU - Vaughn S. Cooper AU - Jennifer M. Bomberger TI - Evolution and adaptation of <em>Pseudomonas aeruginosa</em> in the paranasal sinuses of people with cystic fibrosis AID - 10.1101/2020.10.29.359844 DP - 2020 Jan 01 TA - bioRxiv PG - 2020.10.29.359844 4099 - http://biorxiv.org/content/early/2020/10/29/2020.10.29.359844.short 4100 - http://biorxiv.org/content/early/2020/10/29/2020.10.29.359844.full AB - People with the genetic disorder cystic fibrosis (CF) harbor lifelong respiratory infections, with morbidity and mortality frequently linked to chronic lung infections dominated by the opportunistically pathogenic bacterium Pseudomonas aeruginosa. During chronic CF lung infections, a single clone of P. aeruginosa can persist for decades and dominate end-stage CF lung disease due to its propensity to adaptively evolve to the respiratory environment, a process termed “pathoadaptation”. Chronic rhinosinusitis (CRS), chronic inflammation and infection of the sinonasal space, is highly prevalent in CF and the sinuses may serve as the first site in the respiratory tract to become colonized by bacteria that then proceed to seed lung infections. We identified three evolutionary genetic routes by which P. aeruginosa evolves in the sinuses of people with CF, including through the evolution of mutator lineages and proliferative insertion sequences and culminating in early genomic signatures of host-restriction. Our findings raise the question of whether a significant portion of the pathoadaptive phenotypes previously thought to have evolved in response to selective pressures in the CF lungs may have first arisen in the sinuses and underscore the link between sinonasal and lung disease in CF.Graphical abstract and highlightsPseudomonas aeruginosa undergoes adaptive evolution in the sinuses of people with CFOver time, pathoadapted strains display early signatures of genome degradation consistent with recent host restrictionMutations previously thought to occur in CF lungs may have first evolved in sinusesCompeting Interest StatementThe authors have declared no competing interest.