A Genome-Wide Association Analysis Reveals a 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 genomic study 111 B. multivorans sputum isolates from single CF patient through three stages infection including initial incident infection, deep sampling one-year period chronic post-transplant recolonization. reconstructed evolutionary history used lineage-controlled genome-wide association (GWAS) approach to identify genetic variants antibiotic resistance. found that isolate was more susceptible agents antimicrobial classes (β-lactams, aminoglycosides, quinolones), while diversified into distinct lineages reduced susceptibility same agents. The reinfection displayed phenotypic signatures were all specimens. There numerous examples parallel pathoadaptation, in which individual loci, or even codon, independently mutated multiple times. This set loci enriched for functions virulence Our GWAS identified one variant ampD locus (which four times our dataset) resistance β-lactams, two non-synonymous polymorphisms both aminoglycosides quinolones, affecting an araC family transcriptional regulator, times, outer member porin, twice. also recombination analysis minimum 14 events. Parallel pathoadaptive β-lactam over-represented these recombinogenic regions. illustrates power deep, longitudinal coupled lineage-corrected analyses reveal how pathogens adapt their hosts.