Mycobacterium tuberculosis whiB3 and Lipid Metabolism Genes Are Regulated by Host Induced Oxidative Stress.

The physiological state of the human macrophage may impact the metabolism and the persistence of . This pathogen senses and counters the levels of O, CO, reactive oxygen species (ROS), and pH in macrophages. responds to oxidative stress through WhiB3. The goal was to determine the effect of NADPH oxidase (NOX) modulation and oxidative agents on the expression of and genes involved in lipid metabolism (, , and ) in intracellular mycobacteria. Human macrophages were first treated with NOX modulators such as DPI (ROS inhibitor) and PMA (ROS activator), or with oxidative agents (HO and generator system O), and then infected with mycobacteria. We determined ROS production, cell viability, and expression of , as well as genes involved in lipid metabolism. PMA, HO, and O increased ROS production in human macrophages, generating oxidative stress in bacteria and augmented the gene expression of , , , and . Our results suggest that ROS production in macrophages induces oxidative stress in intracellular bacteria inducing expression. This factor may activate the synthesis of reserve lipids produced to survive in the latency state, which allows its persistence for long periods within the host.