**3.2 Leishmaniasis**

Leishmaniasis is an intracellular protozoan disease caused by *Leishmania* parasites. Leishmaniasis is usually prevalent in tropical and subtropical regions of the world [36, 75]. *Leishmania* parasite infects host macrophages, survives in parasitophorous vacuoles of the macrophage, and escapes from the oxidative killing of the parasite by neutralizing the ROS activity. *Leishmania* Fe-SOD can be classified into two types based on their localization: FeSOD-A isoform is localized in mitochondria, and is related to cellular respiration; FeSOD-B1 and FeSOD-B2 are localized in glycosomes and reduce the oxidative stress generated from cellular reactions [37]. *L. major* contains Sod-B1, Sod-B2, and Sod-C genes on chromosome 32 and sod-A gene on chromosome 8. Sod-B1 and Sod-B2 genes are organized in tandem in both *L. chagasi* and *L. donovani*. Metacyclic promastigote of *L. amazonensis*, when lacking one allele of the Sod-A gene, failed to replicate in macrophages and severely attenuated their ability to established the cutaneous lesions in mice. In addition, the reduction of SOD-A expression in parasites resulting in increased susceptibility to oxidative damage. The failure of SODA/sod-A functions in promastigotes compromised their differentiation

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

into axenic amastigotes. Hence, SOD-A promotes *Leishmania* virulence by protecting the parasites against oxidative stress and initiating ROS-mediated signaling mechanisms, which are required to determine infective forms [37]. *L. chagasi* SOD-B1 null mutant parasites are not viable inside host macrophages. Furthermore, parasites lacking one SOD-B1 allele have markedly reduced their viability [38]. Moreover, WT and SOD-B1/Δsodb1 *L. major* promastigotes have equal capacity to establish infection in murine bone marrow macrophages. However, in contrast to WT parasites, *L. major* SOD-B1/Δsodb1 deficient parasites are declined in number over time in macrophages. The results suggesting its normal level of SOD-B1 is required for *L. major* endurance in macrophages and virulence in mice [76]. The Fe-SOD transcript level and enzyme activity are higher in the amastigote than in the promastigote stage of the parasite when treated with nitroprusside and parquet in *L. chagasi* [72]. In *Leishmania*, FeSOD-A appears to be the first line of defense against ROS and is crucial for parasite survival inside macrophages. Antimony (SbIII) resistant *L. (Viannia) brazilensis* (LbSbR) and *L*. (Leishmania) *infantum* (LiSbR) lines express higher FeSOD-A specific enzyme activity compared to wild type control and showed more resistance toward Antimony (SbIII) [77, 78]. Moreover, miltefosine resistant *L. donovani* are able induce the overexpression of *Ld*FeSODA to protects from drug-induced cytotoxicity, reduces superoxide generation, and involves in suppression of oxidative stress-induced programmed cell death by reducing the phosphatidylserine exposure, DNA damage [79, 80]. Increased exposure of *L. donovani* to miltefosine makes resistance due to the release of *Ld*FeSOD-A into the cytosol from mitochondria. This release of *Ld*FeSOD-A into the cytosol or the inhibition of *Ld*FeSOD-A import into the mitochondria makes the mitochondria even more susceptible to oxidative stress due to the accumulation of ROS. Mitochondria of the parasite are more vulnerable to ROS, leading to programmed cell death, emphasizing its role in keeping healthy mitochondria [39].
