The virulence of Vibrio vulnificus is affected by the cellular level of superoxide dismutase activity

The virulence of superoxide dismutase (SOD) mutants of Vibrio vulnificus, as tested by intraperitoneal injection into mice, decreases in the order of sodC mutant, sodA mutant, and sodB mutant lacking CuZnSOD, MnSOD, and FeSOD, respectively. The survival of SOD mutants under superoxide stress also decreases in the same order. The virulence of soxR mutant, which is unable to induce MnSOD in response to superoxide, is similar to that of the sodA mutant, as the survival of the soxR mutant under superoxide stress is similar to that of the sodA mutant. Consistently, the lowered survival of the soxR mutant is complemented not only with soxR but also with sodA. Thus, the virulence of V. vulnificus is significantly affected by the cellular level of SOD activity, and an increase in SOD level through MnSOD induction by SoxR under superoxide stress is essential for virulence.     

Induction of manganese-containing superoxide dismutase is required for acid tolerance in Vibrio vulnificus

The manganese-containing superoxide dismutase (MnSOD) of Vibrio vulnificus, normally detected after the onset of the stationary phase, is expressed during the lag that immediately follows the transfer of cells grown exponentially to a fresh medium acidified to pH 5.0, whereas Fe-containing SOD is constitutively expressed. The signal triggering the growth lag and MnSOD induction therein is not low pH but intracellular superoxide accumulated under these conditions, since addition of a superoxide scavenger not only shortened the lag but also abrogated the MnSOD induction. If the lysine decarboxylase reaction proceeds in the presence of sufficient lysine, the broth is rapidly neutralized to abolish the generation of oxidative stress. Accordingly, the acid tolerance response was examined without the addition of lysine. SoxR regulates MnSOD induction. Lack of MnSOD caused by mutations in soxR or sodA resulted in low tolerance to low pH. The fur mutant derepressing MnSOD showed better tolerance than the wild type. Thus, an increase in total cytosolic SOD activity through MnSOD induction is essential for the cell to withstand the acid challenge. The contribution of cuprozinc-containing SOD to acid tolerance is not significant compared with those of cytosolic SODs.     

Differential activities of the SoxR protein of Escherichia coli: SoxS is not required for gene activation under iron deprivation

When Escherichia coli cells are under superoxide stress, proteins SoxR and SoxS, acting sequentially, control the expression of a set of repair and defense genes. One of these genes, fumC, encoding fumarase C, was reported to be also activated by iron deprivation in a soxRS-dependent manner. However, the same condition failed to induce the expression of a soxS'::lacZ fusion. The expression of acnA (aconitase A) is also activated by SoxR alone when under iron deprivation, but not of sodA (Mn-superoxide-dismutase). SoxR completely inhibited the migration of a DNA fragment containing the promoter region of fumC, in gel-shift experiments. SoxR might bind to a different region than SoxS within the fumC promoter, or an unknown intermediate other than SoxS might be acting. It is possible that the regulatory role of SoxR is more complex than previously considered.     

Two global regulators repress the anaerobic expression of MnSOD in Escherichia coli: Fur (ferric uptake regulation) and Arc (aerobic respiration control)

The expression of sodA, the Escherichia coli gene encoding manganese superoxide dismutase (MnSOD) is induced by aerobiosis and superoxide generators such as paraquat. Analysis of variants expressing sodA in the absence of oxygen has revealed that mutations in genes for two global regulatory systems, Fur (ferric uptake regulation) and Arc (aerobic respiration control), are simultaneously required for the expression of sodA in anaerobiosis. The Fur protein still represses sodA in an iron-dependent fashion in aerobiosis. Moreover, all mutants remain inducible by paraquat, indicating that the positive control of SoxR, which mediates the response to superoxide in E. coli, is still operative. Thus, in addition to the response to the superoxide-mediated oxidative stress which depends on SoxR, two global controls regulate MnSOD expression: ArcA couples MnSOD expression to respiration, and Fur couples it to the intracellular concentration of iron.     

Mercury induces multiple antibiotic resistance in Escherichia coli through activation of SoxR, a redox-sensing regulatory protein

Sub-inhibitory mercury concentrations are capable of partially activating SoxR, as shown by the augmented expression of a soxS′::lacZ fusion, and a diminished sensitivity to antibiotics caused by mercury treatment. Mercury may elevate the intracellular concentration of superoxide or perhaps act as a putative metal ligand for SoxR.