1887

Abstract

spp. are emerging pathogens in patients with cystic fibrosis (CF) and spp. caused infections are associated with more severe disease outcomes and high intrinsic antibiotic resistance. While conventional CF pathogens are studied extensively, little is known about the genetic determinants leading to antibiotic resistance and the genetic adaptation in spp. infections. Here, we analysed 101 spp. genomes from 51 patients with CF isolated during the course of up to 20 years of infection to identify within-host adaptation, mutational signatures and genetic variation associated with increased antibiotic resistance. We found that the same regulatory and inorganic ion transport genes were frequently mutated in persisting clone types within and between species, indicating convergent genetic adaptation. Genome-wide association study of six antibiotic resistance phenotypes revealed the enrichment of associated genes involved in inorganic ion transport, transcription gene enrichment in β-lactams, and energy production and translation gene enrichment in the trimethoprim/sulfonamide group. Overall, we provide insights into the pathogenomics of spp. infections in patients with CF airways. Since emerging pathogens are increasingly recognized as an important healthcare issue, our findings on evolution of antibiotic resistance and genetic adaptation can facilitate better understanding of disease progression and how mutational changes have implications for patients with CF.

Funding
This study was supported by the:
  • RegionH Rammebevilling (Award R144-A5287)
    • Principle Award Recipient: HelleK. Johansen
  • Savvaerksejer Jeppe Juhl og Hustru Ovita Juhls Mindelegat
    • Principle Award Recipient: HelleK. Johansen
  • Danmarks Frie Forskningsfond (Award FTP-4183-00051)
    • Principle Award Recipient: HelleK. Johansen
  • Novo Nordisk Fonden (Award NNF15OC0017444)
    • Principle Award Recipient: HelleK. Johansen
  • Lundbeckfonden (Award R167-2013-15229)
    • Principle Award Recipient: HelleK. Johansen
  • Rigshospitalets Rammebevilling (Award 2015-17 (R88-A3537))
    • Principle Award Recipient: HelleK. Johansen
  • Novo Nordisk Fonden (Award NNF12OC1015920)
    • Principle Award Recipient: HelleK. Johansen
  • Danmarks Grundforskningsfond (Award 126)
    • Principle Award Recipient: NotApplicable
  • Danish Cystic Fibrosis Association (Cystisk Fibrose Foreningen)
    • Principle Award Recipient: MigleGabrielaite
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2021-07-07
2021-07-29
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