Dl. Piddington et al., Cu,Zn superoxide dismutase of Mycobacterium tuberculosis contributes to survival in activated macrophages that are generating an oxidative burst, INFEC IMMUN, 69(8), 2001, pp. 4980-4987
Macrophages produce reactive oxygen species and reactive nitrogen species t
hat have potent antimicrobial activity. Resistance to killing by macrophage
s is critical to the virulence of Mycobacterium tuberculosis. M. tuberculos
is has two genes encoding superoxide dismutase proteins, sodA and sodC. Sod
C is a Cu,Zn superoxide dismutase responsible for only a minor portion of t
he superoxide dismutase activity of M. tuberculosis. However, SodC has a li
poprotein binding motif, which suggests that it may be anchored in the memb
rane to protect M. tuberculosis from reactive oxygen intermediates at the b
acterial surface. To examine the role of the Cu,Zn superoxide dismutase in
protecting M. tuberculosis from the toxic effects of exogenously generated
reactive oxygen species, we constructed a null mutation in the sodC gene. I
n this report, we show that the M. tuberculosis sodC mutant is readily kill
ed by superoxide generated externally, while the isogenic parental M. tuber
culosis is unaffected under these conditions. Furthermore, the sodC mutant
has enhanced susceptibility to killing by gamma interferon (IFN-gamma)-acti
vated murine peritoneal macrophages producing oxidative burst products but
is unaffected by macrophages not activated by IFN-gamma or by macrophages f
rom respiratory burst-deficient mice. These observations establish that the
Cu,Zn superoxide dismutase contributes to the resistance of M. tuberculosi
s against oxidative burst products generated by activated macrophages.