Non-stop evolution of persistent bacterial infections in the cystic fibrosis lung

HICKMAN RA; COLQUE CA; FRIMODT-MØLLER J; SMANIA AM; MOLIN S; JOHANSEN HK

Congreso; 16th International Conference on Pseudomonas; 2017

Understanding genomic evolution in cystic fibrosis (CF) patients chronically infected with Pseudomonas aeruginosa may help with optimizing antibiotic treatments to delay the need for lung transplantation. From adaptation laboratory experimentation, late stage bacterial evolution is often characterized by loss of diversity and spontaneous mutation development, however little is known about late stage in-vivo bacterial evolution.To explore this, we sequenced the genomes of 14 P. aeruginosa isolates obtained in different time points from a Danish chronically infected CF patient to establish genes that were frequently mutated among the 152 genes related to antimicrobial resistance. To assess population mutational frequency in 19 known antibiotic resistance and pathoadaptive genes, we performed direct whole gene analysis on sputum samples from two chronically infected patients undergoing 14-days hospital intravenous antibiotic therapy.Our results show that evolution is still occurring during antibiotic treatment and that there is selection and counter-selection of non-synonymous mutations. The full implication of these results is yet to be elucidated. But understanding the driving force of in-vivo evolution and utilizing antimicrobial treatment strategies that take advantage of evolutionary traits could help clinicians to optimise treatment strategies and allow patients to have better clinical outcomes.