Burkholderia pseudomallei is the causative agent of melioidosis and represents a potential bioterrorism
threat. In this study, the transcriptomic responses of B. pseudomallei infection of a human macrophage cell model
were investigated using whole-genome microarrays. Gene expression profiles were compared between infected
THP-1 human monocytic leukemia cells with or without treatment with Daboia russelli russelli daboiatoxin (DRRDbTx)
or ceftazidime (antibiotic control). Microarray analyses of infected and treated cells revealed differential upregulation
of various inflammatory genes such as interleukin-1 (IL-1), IL-6, tumor necrosis factor-alpha (TNF-α),
cyclooxygenase (COX-2), vascular endothelial growth factor (VEGF), chemokine C-X-C motif ligand 4 (CXCL4),
transcription factor p65 (NF-kB); and several genes involved in immune and stress responses, cell cycle, and lipid
metabolism. Moreover, following DRR-DbTx treatment of infected cells, there was enhanced expression of the tolllike
receptor 2 (TLR-2) mediated signaling pathway involved in recognition and initiation of acute inflammatory
responses. Importantly, we observed that highly inflammatory cytokine gene responses were similar in infected cells
exposed to DRR-DbTx or ceftazidime after 24 h. Additionally, there were increased transcripts associated with cell
death by caspase activation that can promote host tissue injury. In summary, the transcriptional responses during B.
pseudomallei infection of macrophages highlight a broad range of innate immune mechanisms that are activated
within 24 h post-infection. These data provide insights into the transcriptomic kinetics following DRR-DbTx treatment
of human macrophages infected with B. pseudomallei.