Comparison of clinical and microbiological features between mucoid and non-mucoid <i>Pseudomonas aeruginosa</i> in non-cystic fibrosis bronchiectasis

Mucoid <i>Pseudomonas aeruginosa</i> is frequently isolated from patients with non-cystic fibrosis bronchiectasis (NCFB), yet the clinical and microbiological consequences of this phenotype remain unclear. In this retrospective study, we analyzed 66 patients with NCFB from whom <i>P. aeruginosa</i> was isolated between 2021 and 2024 to compare mucoid and non-mucoid isolates. Among the patients, 32 harbored mucoid and 34 non-mucoid isolates. Compared with patients with non-mucoid isolates, those with mucoid isolates had poorer lung function (FEV₁ % predicted: 52.3 ± 15.7 vs 63.8 ± 17.2; <i>P</i> = 0.006), more frequent exacerbations (2.4 ± 1.3 vs 1.5 ± 1.0 per year; <i>P</i> = 0.002), a faster annual FEV₁ decline (-2.9% ± 2.1% vs -1.6 % ± 1.8% predicted; <i>P</i> = 0.01), more severe radiological disease, and higher treatment burden. Antimicrobial susceptibility profiles and multidrug resistance rates were similar between the groups. However, mucoid isolates showed significantly greater adhesion to airway epithelial cells but lower cytotoxicity than non-mucoid isolates. Time-kill assays revealed a higher tolerance of mucoid isolates to ceftazidime, ciprofloxacin, and tobramycin, with comparable killing observed only for colistin. RT-qPCR analysis revealed that mucoid isolates exhibited significant upregulation of alginate biosynthesis genes, alongside downregulation of motility-associated genes and T2SS/T3SS virulence genes. These findings indicate that mucoid <i>P. aeruginosa</i> infection in NCFB is linked to more severe clinical outcomes and enhanced antibiotic tolerance. Targeted therapeutic strategies addressing the unique biology of mucoid <i>P. aeruginosa</i> may be warranted in NCFB management.IMPORTANCEMucoid <i>Pseudomonas aeruginosa</i> is frequently isolated from patients with non-cystic fibrosis bronchiectasis (NCFB) and is associated with persistent airway infection and difficult-to-treat infections, yet it has been studied far less in NCFB than in cystic fibrosis. The study provides new insights into the biological adaptations of mucoid strains, demonstrating their capacity to persist in the airway and evade standard antimicrobial therapies. Our findings also suggest that conventional antimicrobial susceptibility testing may not fully reflect the clinical challenges posed by mucoid strains. These results highlight the need for improved diagnostic and therapeutic strategies tailored to the distinctive characteristics of mucoid <i>P. aeruginosa</i> in bronchiectasis.