Genomic landscape and phylogenetic insights of <i>Burkholderia pseudomallei</i> over two decades in southern China and its global surveillance

Melioidosis, caused by Burkholderia pseudomallei, is an endemic infectious disease with high mortality in tropical and subtropical regions. Large-scale epidemiological data remain insufficient in China, while comprehensive data integrating genomic epidemiology are rare worldwide. Herein, performed a retrospective analysis of 554 culture-confirmed melioidosis cases in southern China from 2003 to 2022. Genomic characteristics and their relationship with antimicrobial susceptibility and clinical characteristics were analyzed via whole genome sequencing. Core-genome SNP phylogenies were constructed from recombination-masked alignments and compared them with 3,573 publicly available global B. pseudomallei genomes to define their population structure and phylogeographic patterns. Melioidosis predominantly affected male patients (86.8%, 481/554) and those aged 45 -64 years (57.7%). Bacteremia (OR=5.91, p<0.001), diabetes mellitus (OR=2.27, p=0.008), and pulmonary infection (OR=2.26, p=0.005) were identified as risk factors for mortality. Antimicrobial susceptibility testing showed B. pseudomallei exhibited high in vitro susceptibility to imipenem (100%) and ceftazidime (99.6%). Pan-genome analysis confirmed chromosomal functional compartmentalization of the bipartite genome, and genome-wide association study identified high-confidence genetic markers (OR >3 or <0.33) significantly associated with mortality and bacteremia. Furthermore, global phylogenomic analysis identified 10 evolutionary clusters; Chinese isolates were significantly enriched in Cluster 1, a clade shared with Thai strains, and were phylogenetically distinct from Cluster 5, as predominantly composed of Australian isolates. In summary, this large-scale genomic and clinical analysis provides the most comprehensive overview of melioidosis in southern China. The genomic analysis highlighted substantial regional and global genetic diversity, and phylogeographic structuring of B. pseudomallei, underscoring the importance of continued genomic surveillance.