Ahp deficiency-induced redox imbalance leads to metabolic alterations in E. coli

Alkyl hydroperoxide reductase (Ahp) is the primary scavenger of endogenous hydrogen peroxide in Escherichia coli (E. coli). Ahp-deficient strains have been found to have high reactive oxygen species (ROS) levels, sufficient to cause cell damage. However, the exact role and underlying mechanisms of Ahp deficiency-induced cell damage remain largely unknown. Here, the E. coli MG1655 Delta Ahp mutant strain was constructed as a model of deficiency to assess its role. The cells of the Delta Ahp strain were found to be significantly longer than those of the wild strain, with elevated ROS and hydrogen peroxide (H2O2) levels. Proteome, redox proteome and metabolome analyses were performed to systematically present a global and quantitative profile and delineate the redox signaling and metabolic alterations at the proteome, metabolome, and cysteine oxidation site levels. The mul-tiomics data revealed that Ahp deficiency disrupted the redox balance, activated the OxyR system, upregulated oxidative defense proteins and inhibited the TCA cycle to some extent. Surprisingly, the mutant strain shifted from aerobic respiration to anaerobic respiration and fermentation during the logarithmic phase in the presence of sufficient O2. The acid resistance system was activated to mitigate the effect of excessive acid produced by fermentation. Taken together, the results of this study demonstrated that Ahp deficiency triggered cellular redox imbalance and regulated metabolic pathways to confer resistance to submicromolar intracellular H2O2 levels in E. coli.

Automated summary

This study investigated the role and underlying mechanisms of Ahp deficiency-induced cell damage in Escherichia coli. The results demonstrated that Ahp deficiency disrupted the redox balance, activated oxidative defense proteins and inhibited the TCA cycle. Surprisingly, the mutant strain shifted from aerobic respiration to anaerobic respiration and fermentation, and activated the acid resistance system to mitigate the effect of excessive acid produced by fermentation.