Genomic insights into the rapid rise of Pseudomonas aeruginosa ST463: A high-risk lineage’s adaptive strategy in China

High-risk lineages of Pseudomonas aeruginosa pose a serious threat to public health, causing severe infections with high mortality rates and limited treatment options. The emergence and rapid spread of the high-risk lineage ST463 in China have further exacerbated this issue. However, the basis of its success in China remains unidentified. In this study, we analyzed a comprehensive dataset of ST463 strains from 2000 to 2023 using whole genome sequencing to unravel the epidemiological characteristics, evolutionary trajectory, and antibiotic resistance profiles. Our findings suggest that ST463 likely originated from a single introduction from North America in 2007, followed by widespread domestic dissemination. Since its introduction, the lineage has undergone significant genomic changes, including the acquisition of three unique regions that enhanced its metabolism and adaptability. Frequent recombination events, along with the burden of bacteriophages, antibiotic resistance genes, and the spread of c1-type (blaKPC-2) plasmid-carrying strains, have played crucial roles in its expansion in China. Mutation analysis reveals adaptive responses to antibiotics and selective pressures on key virulence factors, indicating that ST463 is evolving toward a more pathogenic lifestyle.