Lipid modification of the Cu,Zn superoxide dismutase from Mycobacterium tuberculosis

The leader sequence of Mycobacterium tuberculosis Cu,Zn superoxide dismutas e (Cu,ZnSOD) contains a prokaryotic membrane lipoprotein attachment site. I n the present study. we have found that the protein, which exhibits detecta ble SOD activity, is lipid-modified and associated with the bacterial membr ane when expressed either in Al. tuberculosis or in Escherichia coli. These results provide the first demonstration of lipid modification of a Cu,ZnSO D. An analysis of the sodC genes present in available databases indicates t hat the same signal for lipid modification is also present in the sodC gene products from other mycobacteria and Gram-positive bacteria and, uniquely, in two distinct sodC gene products from the Gram-negative bacterium Salmon ella typhimurium. Evidence is also provided for an up-regulation of M. tube rculosis sodC in response to phagocytosis by human macrophages, suggesting that Cu,ZnSOD is involved in the mechanisms that facilitate mycobacterial i ntracellular growth.