Burkholderia pseudomallei quorum sensing molecule 3-hydroxy-C₁₀ HSL, triggers organelle stress and inflammatory...

Burkholderia pseudomallei, the causative agent of melioidosis, is a recognised bioterrorism threat. This microorganism produces a key quorum molecule, 3-Hydroxy-C₁₀ homoserine lactone (3-OH-C₁₀ HSL), which has shown to modulate host immune responses. This study investigated the impact of 3-Hydroxy-C₁₀ HSL on A549 cell line, with a focus on organelle stress and inflammatory responses. Treatment with 3-Hydroxy-C₁₀ HSL (100 μM, 2 h) induces a significant elevation of cytosolic calcium and endoplasmic reticulum (ER) stress, evidenced by BiP upregulation and activation of the PERK-CHOP axis, indicating activation of the unfolded protein response (UPR). Mitochondrial function was compromised, as shown by reduced ATP production, loss of mitochondrial membrane potential (MMP), and elevated mitochondrial ROS generation. Furthermore, lysosomal dysfunction was observed through decreased acridine orange puncta, along with TFEB upregulation and LAMP1 downregulation. Gene expression analysis (10 μM, 6 h) revealed activation of the inflammasome pathway, with increased expression of NLRP3, NLRC4, IL-1β, and IL-18, and enhanced secretion of pro-inflammatory cytokines IL-6, TNF- α, and INF- γ. Overall, 3-Hydroxy-C₁₀ HSL disrupts host cellular homeostasis and induces inflammatory stress, providing novel insights into the molecular mechanisms underlying B. pseudomallei mediated pathogenesis.