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

Aims
We aimed to investigate phenotypic and genomic traits of three Cupriavidus spp. isolates recovered from people with cystic fibrosis (PWCF). These bacteria are recognised 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 ARGs with high homology to well-characterised 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 P. aeruginosa. More detailed investigation of clinical Cupriavidus isolates is needed for full understanding of the risk they pose to PWCF.