Impact of ROS-Induced Damage of TCA Cycle Enzymes on Metabolism and Virulence of Salmonella enterica serovar Typhimurium

Discussion Reactive oxygen species (ROS) are generated intrinsically in bacteria (i) by the respiratory chain, (ii) by indirect action of antibiotics, or (iii) are produced by phagocytes combating pathogens. ROS damage DNA and other macromolecules, resulting in growth restriction and/or killing of bacteria. We elucidate how oxidative stress-induced metabolic perturbations of the primary metabolism reduce bacterial viability and facilitate clearance of pathogens. For the analysis of long-term exposition of STM to ROS we used a mutant strain defective in both cytosolic SODs. Since all three types of ROS should accumulate in STM ΔsodAB, we expected to measure increased abundance of proteins encoded by members of the SoxRS- and OxyRS-regulon, induced by SOA and HPO, respectively (Seo et al., 2015). We demonstrated that long-term oxidative stress in a sodAB deletion strain induces metabolic perturbations in amino acid metabolism and CCM. Metabolic profiling proved the high influence of aconitase inhibition and reduced acnA expression on STM metabolism under oxidative stress, in addition to amino acid auxotrophies reported earlier. As deletion of aconitases, fumarases or succinate dehydrogenases alone did not influence Salmonella virulence in RAW264.7 macrophages or survival of MV (=paraquat) treatment, we conclude that inactivation of those metabolic enzymes does not reduce bacterial viability under oxidative stress. However, although the metabolic profile of ΔsodAB...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research