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Achromobacter spp. genetic adaptation in cystic fibrosis

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 genet...

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Autores principales: Gabrielaite, Migle, Nielsen, Finn C., Johansen, Helle K., Marvig, Rasmus L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Microbiology Society 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8477396/
https://www.ncbi.nlm.nih.gov/pubmed/34232117
http://dx.doi.org/10.1099/mgen.0.000582
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author Gabrielaite, Migle
Nielsen, Finn C.
Johansen, Helle K.
Marvig, Rasmus L.
author_facet Gabrielaite, Migle
Nielsen, Finn C.
Johansen, Helle K.
Marvig, Rasmus L.
author_sort Gabrielaite, Migle
collection PubMed
description 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.
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spelling pubmed-84773962021-09-28 Achromobacter spp. genetic adaptation in cystic fibrosis Gabrielaite, Migle Nielsen, Finn C. Johansen, Helle K. Marvig, Rasmus L. Microb Genom Research Articles 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. Microbiology Society 2021-07-07 /pmc/articles/PMC8477396/ /pubmed/34232117 http://dx.doi.org/10.1099/mgen.0.000582 Text en © 2021 The Authors https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License.
spellingShingle Research Articles
Gabrielaite, Migle
Nielsen, Finn C.
Johansen, Helle K.
Marvig, Rasmus L.
Achromobacter spp. genetic adaptation in cystic fibrosis
title Achromobacter spp. genetic adaptation in cystic fibrosis
title_full Achromobacter spp. genetic adaptation in cystic fibrosis
title_fullStr Achromobacter spp. genetic adaptation in cystic fibrosis
title_full_unstemmed Achromobacter spp. genetic adaptation in cystic fibrosis
title_short Achromobacter spp. genetic adaptation in cystic fibrosis
title_sort achromobacter spp. genetic adaptation in cystic fibrosis
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8477396/
https://www.ncbi.nlm.nih.gov/pubmed/34232117
http://dx.doi.org/10.1099/mgen.0.000582
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