Genome mining, antibacterial activity, and metabolomic profiling reveal the biosynthetic potential of Burkholderia glumae isolates from Thailand with activity against clinically important bacterial pathogens

The increasing prevalence of antimicrobial resistance has underscored the need for novel antimicrobial agents. Members of the genus Burkholderia produce a diverse array of antimicrobial metabolites; however, the biosynthetic potential of Burkholderia glumae, a plant pathogen, remains relatively underexplored. In this study, we investigated the biosynthetic potential, antibacterial activity, and metabolomic profiles of 16 B. glumae isolates collected from Thailand. Genome mining using antiSMASH and DeepBGC identified 14-17 and 40-51 biosynthetic gene clusters (BGCs) per genome, respectively. Multiple conserved BGC classes were detected across all isolates, including terpene-, polyketide-, and nonribosomal peptide-associated clusters. DeepBGC further predicted that 22-32 BGCs per isolate were associated with antibacterial activity. Phenotypic screening using soft-agar overlay assays on LB agar demonstrated that all 16 isolates displayed antibacterial activity against clinically important bacterial pathogens, including Acinetobacter baumannii, Escherichia coli, and Staphylococcus aureus. Four isolates exhibiting the strongest antibacterial activity were selected for further metabolomic analysis. Untargeted LC-MS/MS profiling of extracts from inoculated and uninoculated LB agar plates identified 68 putatively annotated antimicrobial-related metabolites shared among all four isolates and significantly enriched relative to the uninoculated controls (fold change > 2, p < 0.05). These metabolites belonged to diverse chemical classes, including macrolactams, triterpene saponins, triterpenoids, hydroxyquinolones, phenolic glycosides, and cyclic depsipeptides. Macrolactams represented the most frequently detected metabolite class, whereas triterpene saponins exhibited the highest enrichment relative to control LB agar without bacterial inoculation. Toxoflavin, reumycin, and bactobolin A were not detected in extracts from cultures grown on LB agar at 37 °C for 24 h. These findings, which demonstrate that B. glumae isolates from Thailand possess diverse biosynthetic capabilities and antibacterial activity against clinically important bacterial pathogens, highlight the potential of these isolates as a source of bioactive metabolites for future efforts in antimicrobial agent discovery.