Achromobacter spp. genetic adaptation in cystic fibrosis

Migle Gabrielaite*, Finn C. Nielsen, Helle K. Johansen, Rasmus L. Marvig

*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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Abstract

Achromobacter spp. are emerging pathogens in patients with cystic fibrosis (CF) and Achromobacter 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 Achromobacter spp. infections. Here, we analysed 101 Achromobacter 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 Achromobacter 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 Achromobacter 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.

OriginalsprogEngelsk
Artikelnummer000582
TidsskriftMicrobial genomics
Vol/bind7
Udgave nummer7
Antal sider13
ISSN2057-5858
DOI
StatusUdgivet - 2021

Bibliografisk note

Funding Information:
This work was supported by the Danish Cystic Fibrosis Association (Cystisk Fibrose Foreningen) and the Danish National Research Foundation (grant number 126). HKJ was supported by The Novo Nordisk Foundation as a clinical research stipend (NNF12OC1015920), by Rigshospitalets Rammebevilling 2015-17 (R88-A3537), by Lundbeckfonden (R167-2013-15229), by Novo Nordisk Fonden (NNF15OC0017444), by RegionH Rammebevilling (R144-A5287) by Independent Research Fund Denmark / Medical and Health Sciences (FTP-4183-00051) and by ‘Savværksejer Jeppe Juhl og Hustru Ovita Juhls mindelegat’.

Funding Information:
This work was supported by the Danish Cystic Fibrosis Association (Cystisk Fibrose Foreningen) and the Danish National Research Foundation (grant number 126). HKJ was supported by The Novo Nordisk Foundation as a clinical research stipend (NNF12OC1015920), by Rigshospitalets Rammebevilling 2015-17 (R88-A3537), by Lundbeckfonden (R167-2013-15229), by Novo Nordisk Fonden (NNF15OC0017444), by RegionH Rammebevilling (R144-A5287) by Independent Research Fund Denmark / Medical and Health Sciences (FTP-4183-00051) and by ?Savv?rksejer Jeppe Juhl og Hustru Ovita Juhls mindelegat?.

Publisher Copyright:
© 2021 The Authors.

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