Genomic divergence between clinical and environmental Pseudomonas aeruginosa within ST-matched high-risk and sporadic lineages: A case study.

Pseudomonas aeruginosa is a major opportunistic pathogen and a leading cause of nosocomial infections in the Asia-Pacific region. This comparative genomic case study investigated 18 P. aeruginosa isolates, categorized into nine ST-matched sets to minimize phylogenetic noise and identify genomic divergence between clinical and environmental habitats. The isolates represent both globally distributed high-risk clones (ST235, ST357, ST308) and sporadic lineages (ST274, ST316, ST381). The genomes possessed a mean size of 6.7 ± 0.2 Mbp and shared a core genome of 4639 genes. Virulence profiling revealed a strictly mutually exclusive distribution of exoU (cytotoxic) and exoS (invasive) genotypes. While exoU was detected in both clinical and environmental isolates, the spcU chaperone gene was entirely absent in the environmental group. Even among clinical exoU-positive isolates, spcU was only present in 42.8% (3/7) of the strains, indicating that the complete exoU-spcU locus is not consistently maintained in either setting. Clinical isolates generally harbored a higher density of acquired antimicrobial resistance genes (ARGs), including determinants such as qnrVC1 and blaVEB-9, whereas the blaNDM-1 carbapenemase and chromosomal mutations (gyrA T83I; basR L71R) were maintained across both ecological sources. Mobile genetic elements (MGEs) were the primary drivers of accessory genome divergence, with high-risk lineages exhibiting a robust resistance backbone regardless of their origin. As a targeted, hypothesis-generating case study without formal statistical testing, these results are consistent with lineage-specific genomic divergence rather than a confirmed species-wide evolutionary transition. Our findings underscore that environmental reservoir in the Asia-Pacific harbor high-risk clones with significant resistance potential, necessitating sustained regional genomic surveillance across diverse habitats.