Genomic epidemiology and resistance determinants of Pseudomonas aeruginosa in bronchiectasis across China: a multicentre study.
Abstract
Objectives
To characterise the genomic epidemiology and resistance determinants of bronchiectasis-associated Pseudomonas aeruginosa in a multicentre cohort.
Methods
We analysed 306 first non-duplicate P. aeruginosa isolates (2019-2021). Antimicrobial susceptibility was determined by broth microdilution and mucoid phenotype was recorded. Whole-genome sequencing was used for MLST, core-genome SNP phylogeny, resistance and virulence gene screening, and amino-acid variation in gyrA/gyrB/parC/parE, oprD, efflux regulators and mucoidy regulators (mucA, algU, mucB and mucD).
Results
Mucoid isolates comprised 68.6% of the collection. 201 sequence types indicated a polyclonal population without geographic or phenotype-specific clustering. Resistance was highest to levofloxacin (41.5%) and ciprofloxacin (39.2%), and lowest to amikacin (0.3%). Multidrug-resistant isolates accounted for 16.3%. Species-associated determinants were near-universal (blaPAO, aph(3')-IIb, fosA, catB7 and blaOXA-50), whereas acquired genes were uncommon. Among fluoroquinolone-resistant isolates, 97.0% carried amino-acid changes in at least one quinolone target gene, with canonical QRDR hotspots alongside additional variants such as gyrA (S912_E913del) and gyrB (H148N). In imipenem-resistant isolates, oprD variation was detected in 98.1% (52/53). Mucoid isolates were enriched for mucA variation (88.6% vs 57.3%). Virulence profiling revealed a largely conserved repertoire characterised by alginate regulation, quorum sensing and secreted toxins, with an exoS-predominant T3SS and broadly distributed T6SS components.
Conclusions
Bronchiectasis-associated P. aeruginosa constitutes a polyclonal, genetically heterogeneous population. Non-susceptibility predominantly reflects intrinsic and adaptive genomic mechanisms. Given the high fluoroquinolone resistance observed, treatment should be guided by local resistance patterns and isolate-specific susceptibility results.