Highly diverse dynamics of Pseudomonas aeruginosa colonization from initial detection in cystic fibrosis patients: A 7-year longitudinal genetic diversity study

In cystic fibrosis (CF), Pseudomonas aeruginosa (Pa) is a major pathogen that can persistently colonize patients. Genetic studies showed a high diversity of Pa, the success of widespread or 'international' clones and described epidemic clones in CF and Epidemic High-Risk (ERH) clones. Here, we characterized Pa genetic diversity over time after first colonization in CF patients, with the aim of accurately describing the dynamics of colonization in a context of scarce longitudinal studies including the first isolated Pa strain. Results represent the first genotyping data available for CF Pa in France. Forty-four CF patients with a first Pa colonization were included; 265 strains collected over 7 years in these patients were genotyped by multiplex rep-PCR, multilocus sequence typing, pulsed-field gel electrophoresis and/or whole genome sequencing. Forty-one sequence types were identified: 4 were unknown, 22 never previously reported for CF patients, and 6 corresponded to widespread clones colo-nizing 16 patients (36%). Unrelated strains were identified in 41 patients (93%). Twenty-six patients (59%) presented a recurrence during the study period. No specific clones were associated with transient, recurrent or persistent colonization. Our longitudinal study revealed that 9 of the 26 patients with recurrence (35%) harbored strains of different genotypes. Great genetic diversity was observed among initial Pa isolates excluding any cross -transmission. Persistent colonization may appear more complex than expected, imitating persistence, with successive colonization events by unrelated Pa.