Optical spectrum of HDE 245770 /A0535 + 26/

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<i>Pseudomonas aeruginosa</i> airway colonization and infection are major drivers of chronic obstructive pulmonary disease (COPD) acute exacerbations, yet its adaptive evolution in the COPD airway remains poorly understood. Here, six serial <i>P. aeruginosa</i> strains were isolated over a 5-month interval from a single COPD patient: two initial isolates (SCPa03-1 and SCPa03-2) from one sputum sample and four subsequent isolates (SCPa12-1, SCPa12-2, SCPa12-3, and SCPa12-4) from another. Of them, SCPa03-1, SCPa12-1, and SCPa12-2 exhibited a non-mucoid phenotype, while SCPa03-2, SCPa12-3, and SCPa12-4 were mucoid. All isolates were resistant to most <i>β</i>-lactam antibiotics, including imipenem, but susceptible to amikacin and gentamicin. Notably, three mucoid strains were susceptible to meropenem. Genomic and phylogenetic analysis revealed that all isolates were clonally related, belonged to ST274, and were closely related to the globally prevalent high-risk ST274 clone. Sequence analysis and qRT-PCR suggested that their imipenem resistance may be associated with <i>ampC</i> overexpression and <i>oprD</i> mutations, while reduced ciprofloxacin susceptibility likely stemmed from <i>gyrA</i>/<i>gyrB</i> mutations and acquisition of <i>crpP</i>-harboring ICEs. Despite a shared <i>mucA</i> frameshift mutation, secondary mutations in <i>prc</i> (SCPa03-1) and <i>algU</i> (SCPa12-1, SCPa12-2) likely accounted for the non-mucoid phenotype. Relative to PAO1, all isolates showed reduced growth, diminished pyoverdine, attenuated <i>Galleria mellonella</i> virulence, and increased pyocyanin. Besides, three mucoid strains exhibited slower growth, reduced serum resistance, and attenuated virulence compared with non-mucoid counterparts, suggesting adaptive trade-off during host adaptation. Four late-stage isolates showed enhanced pyoverdine production and improved growth under iron limitation, indicating progressive airway adaptation to the iron-restricted airway niche.IMPORTANCE<i>Pseudomonas aeruginosa</i> is a leading cause of chronic airway infection and poses a severe clinical threat when it develops carbapenem resistance. While the adaptive evolution of <i>P. aeruginosa</i> has been well characterized in cystic fibrosis, its evolutionary patterns during chronic infection in patients with chronic obstructive pulmonary disease (COPD) remain poorly understood. Here, we analyzed six imipenem-resistant <i>P. aeruginosa</i> isolates sequentially recovered from a single COPD patient. Integrated genomic and phenotypic analyses demonstrated that the high-risk clone ST274 diversified extensively within the host, with genetic variations strongly associated with enhanced airway persistence. These findings advance our understanding of how carbapenem-resistant <i>P. aeruginosa</i> adapts during chronic COPD infection and provide new insights into resistance evolution and adaptive strategies that may inform the control of drug-resistant chronic respiratory infections.

Abstract: PubMed · Datensatz