Emergence and impact of oprD mutations in Pseudomonas aeruginosa strains in cystic fibrosis

•P. aeruginosa strain sub-lineages with specific oprD variants have spread between patients.•The oprD variants are important contributors to carbapenem resistance.•People infected with the strain sub-lineages had a lower baseline lung function.•Infection with the sub-lineages was not associated with a worse prognosis. Antimicrobial resistance in cystic fibrosis (CF) Pseudomonas aeruginosa airway infection is complex and often attributed to chromosomal mutations. How these mutations emerge in specific strains or whether particular gene mutations are clinically informative is unclear. This study focused on oprD, which encodes an outer membrane porin associated with carbapenem resistance when it is downregulated or inactivated. Determine how mutations in oprD emerge in two prevalent Australian shared CF strains of P. aeruginosa and their clinical relevance. The two most common shared CF strains in Queensland were investigated using whole genome sequencing and their oprD sequences and antimicrobial resistance phenotypes were established. P. aeruginosa mutants with the most common oprD variants were constructed and characterised. Clinical variables were compared between people with or without evidence of infection with strains harbouring these variants. Frequently found nonsense mutations arising from a 1-base pair substitution in oprD evolved independently in three sub-lineages, and are likely major contributors to the reduced carbapenem susceptibility observed in the clinical isolates. Lower baseline FEV1 %predicted was identified as a risk factor for infection with a sub-lineage (odds ratio=0.97; 95% confidence interval 0.96-0.99; p