The Role of Superoxide Dismutase in the Survival of <i>Mycobacterium tuberculosis</i> in Macrophages

Abstract

SUMMARY:There is a large amount of information available regarding the chemical structure and biological activity of superoxide dismutase (SOD), which is abundantly generated by Mycobacterium tuberculosis in the early stages of growth. SOD is a strong superoxide radical scavenger, which plays a significant role in resisting oxidative stress. On the other hand, SOD mutant strains have been constructed to define the role of this molecule in the immune response to M. tuberculosis infection. These studies have suggested that the absence or attenuation of SOD can motivate innate immunity and SOD avoid destruction or growth inhibition of M. tuberculosis. For detailed investigation of how SOD proteins aid M. tuberculosis survival within macrophages, we cloned 2 SOD genes (SODA and SODC) from the M. tuberculosis H37Rv genome, overexpressed, identified, and purified the proteins, and then exposed macrophages to the proteins. Following this, we assessed NO production, the secretion of cytokine interferon-g (IFN-g) and intercellular adhesion molecule-1, the expression of IFN-g receptor and Toll-like receptor 2 on the surface of macrophages, and caspase-3 enzyme activity as well as macrophage apoptosis. Our results showed that both SODA and SODC proteins considerably reduced the production of NO and oxygen radicals and impaired cell immunologic function in early infection.

Mycobacterium tuberculosis lipoproteins in virulence and immunity – fighting with a double‐edged sword

“…They indirectly contribute to infection of macrophages and survival of M. tuberculosis through the transport of adhesion and immunomodulatory molecules to the mycobacterial outer membrane, as it has been shown for LppX and LprG. They play a direct role in the endurance of a hostile environment during dormancy by neutralizing toxic substances as suggested for superoxide dismutase SodC and LpqS or are, like RpfB, involved in the resuscitation of M. tuberculosis in order to induce active disease. In addition, some lipoproteins have immunomodulatory functions in the down‐regulation of proinflammatory stimuli during initial infection and dormancy as it has been shown for LpqH and LprN.…”

Proteomic profiling for plasma biomarkers of tuberculosis progression

“…In addition, it has been indicated that the concentration of SOD decreases in patients with pulmonary failure ( 23 ). Furthermore, SOD proteins considerably reduced the production of NO and oxygen radicals and ameliorated impairment in cell immunological function during early infection ( 24 ). The present study demonstrated that SOD1 levels were significantly lower in patients with STB, compared with the MTB and NC groups.…”

Reactive species and pathogen antioxidant networks during phagocytosis

“…Fe-SODA was reported to be essential for Mtb growth, and bacteria with reduced Fe-SODA content are largely attenuated (Edwards et al, 2001). Both Fe-SODA and Cu-SODC can inhibit immune functions as well as promote macrophage apoptosis, contributing to bacterial survival by mechanisms independent of O 2 •− dismutation (Liao et al, 2013).…”