Transcriptional profiles of Burkholderia pseudomallei reveal the direct and indirect roles of Sigma E under oxidative stress conditions

Background: Burkholderia pseudomallei, the causative agent of melioidosis, is a Gram-negative bacterium widely distributed in soil and water in endemic areas. This soil saprophyte can survive harsh environmental conditions, even in soils where herbicides (containing superoxide generators) are abundant. Sigma factor E (σ^E) is a key regulator of extra-cytoplasmic stress response in Gram-negative bacteria. In this study, we identified the B. pseudomallei σ^E regulon and characterized the indirect role that σ^E plays in the regulation of spermidine, contributing to the successful survival of B. pseudomallei in stressful environments. Results: Changes in the global transcriptional profiles of B. pseudomallei wild type and σ^E mutant under physiological and oxidative stress (hydrogen peroxide) conditions were determined. We identified 307 up-regulated genes under oxidative stress condition. Comparison of the transcriptional profiles of B. pseudomallei wild type and σ^E mutant under control or oxidative stress conditions identified 85 oxidative-responsive genes regulated by σ^E, including genes involved in cell membrane repair, maintenance of protein folding and oxidative stress response and potential virulence factors such as a type VI secretion system (T6SS). Importantly, we identified that the speG gene, encoding spermidine-acetyltransferase, is a novel member of the B. pseudomallei σ^E regulon. The expression of speG was regulated by σ^E, implying that σ^E plays an indirect role in the regulation of physiological level of spermidine to protect the bacteria during oxidative stress.Conclusion: This study identified B. pseudomallei genes directly regulated by σ^E in response to oxidative stress and revealed the indirect role of σ^E in the regulation of the polyamine spermidine (via regulation of speG) for bacterial cell protection during oxidative stress. This study provides new insights into the regulatory mechanisms by which σ^E contributes to the survival of B. pseudomallei under stressful conditions.