Evolution and dynamics of antibiotic resistance genes in Pseudomonas aeruginosa populations growing in the cystic fibrosis lung

SMANIA AM; SOMMER LM; JOHANSEN HK; HICKMAN RA; MOLIN S; COLQUE CA

Congreso; Congress 2017 of the Danish Microbiological Society; 2017

Understanding bacterial genomic evolution in Pseudomonas aeruginosa (PA) populations infecting cystic fibrosis (CF) patients may help optimizing antibiotic treatment and prolong life expectancy of the patients. In laboratory experiments, bacterial evolution is often characterized by loss of diversity and random mutation accumulation, however little is known about in patient bacterial evolution.We previously sequenced the genomes of 14 hypermutator isolates of PA from a CF patient, spanning 20 years of patient infection history. To investigate antimicrobial resistance genes that are frequently mutated, we analyzed mutation frequencies in 152 genes. Our results revealed high genetic diversity in four genes related to β-lactam resistance (ampC, ftsI, mpl and ampDH3). To assess population allele dynamics for these well-known antibiotic resistance genes, we performed whole gene sequence analysis directly in sputum sample bacterial populations obtained during five years of chronic infection from two CF patients.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 forces of in patient evolution and utilizing antimicrobial treatment strategies that take advantage of a growing understanding of the evolutionary paths could help clinicians to optimise treatment strategies and ensure that patients have better clinical outcomes.