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Global genomic diversity of Pseudomonas aeruginosa in bronchiectasis.
Harrington, N E; Kottara, A; Cagney, K; Shepherd, M J; Grimsey, E M; Fu, T; Hull, R C; Chong, C E; Baker, K S; Childs, D Z; Fothergill, J L; Chalmers, J D; Brockhurst, M A; Paterson, S.
Afiliação
  • Harrington NE; Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, L69 3BX, UK. Electronic address: Niamh.Harrington@liverpool.ac.uk.
  • Kottara A; Division of Evolution and Genomic Sciences, School of Biological Sciences, University of Manchester, M13 9NT, UK.
  • Cagney K; Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, L69 3BX, UK.
  • Shepherd MJ; Division of Evolution and Genomic Sciences, School of Biological Sciences, University of Manchester, M13 9NT, UK.
  • Grimsey EM; Division of Evolution and Genomic Sciences, School of Biological Sciences, University of Manchester, M13 9NT, UK.
  • Fu T; Division of Evolution and Genomic Sciences, School of Biological Sciences, University of Manchester, M13 9NT, UK.
  • Hull RC; Division of Molecular and Clinical Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK.
  • Chong CE; Department of Genetics, University of Cambridge, CB2 3EH Cambridge, UK.
  • Baker KS; Department of Genetics, University of Cambridge, CB2 3EH Cambridge, UK.
  • Childs DZ; Department of Animal and Plant Sciences, University of Sheffield, S10 2TN Sheffield, UK.
  • Fothergill JL; Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, L69 3BX, UK.
  • Chalmers JD; Division of Molecular and Clinical Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK.
  • Brockhurst MA; Division of Evolution and Genomic Sciences, School of Biological Sciences, University of Manchester, M13 9NT, UK.
  • Paterson S; Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, L69 3BX, UK.
J Infect ; 89(5): 106275, 2024 Nov.
Article em En | MEDLINE | ID: mdl-39293722
ABSTRACT

OBJECTIVES:

Pseudomonas aeruginosa is the most common pathogen in the bronchiectasis lung, associated with worsened outcomes. P. aeruginosa genomic studies in this context have been limited to single-country, European studies. We aimed to determine strain diversity, adaptation mechanisms, and AMR features to better inform treatment.

METHODS:

P. aeruginosa from 180 bronchiectasis patients in 15 countries, obtained prior to a phase 3, randomised clinical trial (ORBIT-3), were analysed by whole-genome sequencing. Phylogenetic groups and sequence types were determined, and between versus within patient genetic diversity compared using Analysis of Molecular Variance (AMOVA). The frequency of AMR-associated genes and mutations was also determined.

RESULTS:

A total of 2854 P. aeruginosa isolates were analysed, predominantly belonging to phylogenetic group 1 (83%, n = 2359). Genetic diversity was far greater between than within patients, responsible for >99.9% of total diversity (AMOVA phylogroup 1 df = 145, P < 0.01). Numerous pathways were under selection, some shared with CF (e.g., motility, iron acquisition), some unique to bronchiectasis (e.g., novel efflux pump PA1874). Multidrug resistance features were also frequent.

CONCLUSIONS:

We present a 10-fold increase in the availability of genomic data for P. aeruginosa in bronchiectasis, highlighting key distinctions with cystic fibrosis and potential targets for future treatments.
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Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Filogenia / Pseudomonas aeruginosa / Infecções por Pseudomonas / Variação Genética / Bronquiectasia / Sequenciamento Completo do Genoma Limite: Female / Humans / Male Idioma: En Revista: J Infect Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Filogenia / Pseudomonas aeruginosa / Infecções por Pseudomonas / Variação Genética / Bronquiectasia / Sequenciamento Completo do Genoma Limite: Female / Humans / Male Idioma: En Revista: J Infect Ano de publicação: 2024 Tipo de documento: Article