**2. Superoxide dismutase**

The evolutionary history of metalloenzyme superoxide dismutase (SOD) is aged and has been there before the differentiation of eubacteria from archaea bacteria. It is ubiquitous protein present in all living organisms and plays a vital role in the extreme pressure defense against superoxide radicals in the cell. The SOD catalyzes the conversion of the two molecules of virulent oxygen free radical (O− ) into molecular oxygen (O2) and hydrogen peroxide (H2O2) by using two equivalents of H+ ions [10]. SOD is marked as a strong free radical scavenger that can eliminate the toxic effects of superoxide produced during the reduction of molecular oxygen. SODs enzyme family have been classified based on several factors, and one is on the metal ion. In general, SODs contain the metal cofactor at their catalytic core and are classified into three major groups: copper/zinc (Cu/Zn-SOD) [11, 12], manganese (Mn-SOD) [13], and iron (Fe-SOD) [14–16]. SOD containing MnSOD, FeSOD and CuZnSOD are encrypted

*Superoxide Dismutase: A Key Enzyme for the Survival of Intracellular Pathogens in Host DOI: http://dx.doi.org/10.5772/intechopen.100322*

by the gene sodA, sodB, and sodC, respectively. Nickel (Ni)- and iron-zinc (Fe/Zn) containing isozymes have also been identified in several bacteria [17, 18]. FeSOD has mainly reported in prokaryotes except few protozoan parasites, whereas MnSOD and CuZnSOD are found in both prokaryotes and eukaryotes. All these isoforms were identified based on their diverse sensitivities to cyanide (CN) and H2O2. The Cu, Zn-SOD is extremely sensitive to CN and H2O2 [19]. Mn-SOD is insensitive to CN and H2O2 [20], while Fe-SOD is not sensitive to CN but sensitive to H2O2 [21]. In addition, Mn-SOD and Fe-SOD, both were inhibited by chloroform–ethanol, but Cu, Zn-SOD is insensitive [22].

Moreover, SODs of intracellular bacteria are further classified into three groups based on their localization; Mn- and Fe-cofactor SODs are found in the cytosol. In contrast, the third one of SOD cofactor by Cu-Zn and is attached with periplasm or anchored with the lipid of the outer envelope [23, 24]. Cu/Zn-SOD of bacteria dismutase superoxide produced by host cell during phagocytosis contributes to helping bacterial virulence [25, 26]. Additionally, few families of SODs also use a Ni ion as cofactor at their catalytic core to initiate its functions [27]. A study has shown that superoxide dismutase from *Streptococcus* is capable of making a cofactor substitution with Fe in place of Mn [28]. On the other hand, *Leishmania tropica*, *Trypanosoma brueci*, and *Crithidia fasciculate* have superoxide dismutase, which is insensitivity to cyanide but sensitive to azide and peroxide [29]. SODs of Trypanosomatids are having Fe as a metal cofactor at their catalytic core and are categorized as iron superoxide dismutase (Fe-SOD). Other protozoan parasites also have the same Fe-SOD, such as *Plasmodium falciparum* and *Entamoeba histolytica*, where enzyme-mediated free radical catabolism is fully Fe-SOD dependent [30]. Fe-SOD isoform was first discovered in *Escherichia coli* in 1973 by Yost and Fridovich. Subsequently, the same isoform was characterized in *T. cruzi* in 1977. Like Trypanoredoxin (TR), SODs of *T. cruzi* differ from the mammalian host. Trypanosomatids, other protozoan parasites (*P. falciparum and E. histolytica*), some plants, and Archaea possess only Fe-SOD. However, humans and other mammalian hosts contain Cu/Zn-SOD and Mn-SOD as core metal **Figure 1** [31].

**Figure 1.**

*Schematic representation of SOD localization in intracellular pathogens and SOD chemical reaction. A) Localization of SOD in bacterial pathogens, B) localization of SOD in protozoan and fungal pathogens and C) SOD reaction in mitochondria of protozoan and fungal pathogens.*

This chapter will discuss role of superoxide dismutase in various intracellular pathogens that are belong to protozoan parasites genus *Trypanosoma, Leishmania, Plasmodium* and *Toxoplasma*, bacterial intracellular pathogens belongs to genus *Mycobacterium, Salmonella, Francisella* and *Staphylococcus* and fungal intracellular pathogens belongs to genus *Cryptococcus and Histoplasma* etc.
