A genome-wide association analysis reveals a potential role for recombination in the evolution of antimicrobial resistance in Burkholderia multivorans.

摘要: Cystic fibrosis (CF) lung infections caused by members of the Burkholderia cepacia complex, such as multivorans, are associated with high rates mortality and morbidity. We performed a population genomics study 111 B. multivorans sputum isolates from one CF patient through three stages infection including an early incident isolate, deep sampling one-year period chronic occurring weeks before transplant, post-transplant infection. reconstructed evolutionary history used lineage-controlled genome-wide association (GWAS) approach to identify genetic variants antibiotic resistance. found isolate was basally related rest strains more susceptible antibiotics classes (β-lactams, aminoglycosides, quinolones). The diversified into multiple, distinct lineages showed reduced antimicrobial susceptibility same antibiotics. reinfection derived source were genetically isolates. They also had level in between that identified numerous examples potential parallel pathoadaptation, which multiple mutations locus or even codon. set pathoadaptive loci enriched for functions virulence Our GWAS analysis statistical associations polymorphism ampD resistance β-lactams, polymorphisms araC transcriptional regulator outer membrane porin both aminoglycosides quinolones. Additionally, these independently mutated four, two times, respectively, providing further support pathoadaptation. Finally, we minimum 14 recombination events, observed carrying putative pathoadaptations statistically β-lactam over-represented recombinogenic regions.