Genomic insights and phenotypic characterization of three multidrug resistant Cupriavidus strains from the cystic fibrosis lung

Sean D Kelly, James Butler, Heather Green, Andrew M Jones, Dervla T D Kenna, Sumita Pai, Katie J Muddiman, Trudie A McComb, Briana M Barrand, Vicky Bennett, Gyorgy Fejer, Mathew Upton

Research output: Contribution to journalArticlepeer-review

Abstract

Aims
We aimed to investigate phenotypic and genomic traits of three Cupriavidus spp. isolates recovered from people with cystic fibrosis (PWCF). These bacteria are recognized as emerging pathogens in PWCF.

Methods and results
Using short and long sequencing reads, we assembled three hybrid complete genomes for the genus Cupriavidus, adding to the 45 published currently, describing multipartite genomes and plasmids. The isolates likely represent three different species, and they carry a cumulative total of 30 antibiotic resistance genes with high homology to well-characterized resistance determinants from other bacteria. Multidrug resistance to antibiotics used in CF management was observed in all three isolates. However, two treatments were active across all isolates: cefotaxime and piperacillin/tazobactam. Biofilm formation was only seen at physiological temperatures (37°C) and lost at 20°C and all isolates had low lethality in Galleria mellonella larvae. Isolates demonstrated variable motility, with one non-motile isolate carrying a disrupted flhD transcriptional regulator, abolishing flagella expression.

Conclusions
Our Cupriavidus spp. isolates showed considerable genomic and phenotypic variability that may impact their virulence and treatment in PWCF, where multidrug resistance will negate treatments and biofilm formation and motility play key roles in infection establishment, as seen in CF pathogens like Pseudomonas aeruginosa. More detailed investigation of clinical Cupriavidus isolates is needed for full understanding of the risk they pose to PWCF.
Original languageEnglish
Article numberlxaf093
JournalJournal of Applied Microbiology
Volume136
Issue number5
Early online date17 Apr 2025
DOIs
Publication statusPublished - 31 May 2025

Data Availability Statement

All three genome assemblies and corresponding annotations were submitted to the National Center for Biotechnology Information (NCBI) GenBank database under accession numbers: Cupriavidus sp. H18C1, CP186008; Cupriavidus sp. H18C2, CP186010; and Cupriavidus sp. H19C3, CP184985. Other data that support the findings of this study are available from the corresponding author upon reasonable request.

Funding

The authors acknowledge a PhD Studentship to SDK. that was kindly supported by a grant awarded by the Boomer Esiason Foundation, and donors to University of Plymouth. Molendotech Ltd contributed to the fees for this PhD Studentship. VB. is supported by a studentship from the GW4 Biomed MRC DTP (Grant number MR/N0137941/1).

FundersFunder number
Boomer Esiason Foundation
University of Plymouth
GW4 BioMed Medical Research CouncilMR/N0137941/1

    Keywords

    • biofilm
    • cupriavidus
    • cystic fibrosis
    • hybrid genome assembly
    • motility
    • multi-drug resistance

    ASJC Scopus subject areas

    • Biotechnology
    • Applied Microbiology and Biotechnology

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