Abstract
Superoxide generation is inevitable in aerobic organisms, most of which have developed mechanisms to detoxify superoxides. However, its significance has not been clearly understood in mycobacteria. This study demonstrates that NADH oxidase is the major source of superoxide in Mycobacterium smegmatis and elucidates the involvement of superoxide in M. smegmatis growth. The maximum inhibition of superoxide generation was observed in the presence of diphenyleneiodonium chloride (DPI), an NADH oxidase inhibitor, compared to other standard inhibitors. After incubation for 24 h, the number of colony forming units (CFUs) was reduced by 6.8 log10 compared to the untreated culture. The inhibitory effect of DPI on M. smegmatis was reversed when the same culture was supplemented with menadione and pyrogallol, which are superoxide generators. Thus, this study reports the source of superoxide generation and its involvement in the growth of M. smegmatis.
Highlights
The survival of Mycobacterium tuberculosis (Mtb) the causative agent of tuberculosis inside the phagosomes of macrophages is critical for its virulence (Russell, 2001; Schnappinger et al, 2003; Rohde et al, 2007)
Earlier studies have demonstrated that the level of superoxide production is proportional to the availability of O2 in the environment (Bloomfield and Pears, 2003; Foreman et al, 2003; Buetler et al, 2004; Shi et al, 2008)
Our initial studies using DHE have clearly established that actively growing M. smegmatis bacilli continuously produce superoxide radicals (Figure 2)
Summary
The survival of Mycobacterium tuberculosis (Mtb) the causative agent of tuberculosis inside the phagosomes of macrophages is critical for its virulence (Russell, 2001; Schnappinger et al, 2003; Rohde et al, 2007). Mtb has evolved protective detoxification mechanisms in response to the exogenous oxidative stress encountered inside the host phagocytes. Mtb encounters ROS in the host and overcomes the oxidative stress through multiple thioredoxin systems that function as the antioxidant defense, such as thioredoxin reductase, thioredoxin C, and TPx (Jaeger et al, 2004). These findings support that Mtb possesses a thiol-oxidoreductase system along with a superoxide-detoxifying enzyme (SodA) and an integral membrane protein (DoxX) called the membrane-associated oxidoreductase complex (MRC; Nambi et al, 2015). Earlier reports have suggested that a more oxidizing environment leads to the enhanced growth of M. abscessus as well as Mtb inside macrophages and a reducing environment inhibits their growth (Meylan et al, 1992; Oberley-Deegan et al, 2010)
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