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Infection and Immunity, August 2001, p. 4980-4987, Vol. 69, No. 8
0019-9567/01/$04.00+0 DOI: 10.1128/IAI.69.8.4980-4987.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Cu,Zn Superoxide Dismutase of Mycobacterium
tuberculosis Contributes to Survival in Activated
Macrophages That Are Generating an Oxidative Burst
Debra L.
Piddington,1
Ferric C.
Fang,2
Tracey
Laessig,2
Andrea M.
Cooper,3
Ian M.
Orme,3 and
Nancy A.
Buchmeier1,*
Department of Pathology, University of
California, San Diego, La Jolla, California,1
and Departments of Medicine, Pathology, and Microbiology,
University of Colorado Health Sciences Center,
Denver,2 and Department of
Microbiology, Colorado State University, Fort
Collins,3 Colorado
Received 15 December 2000/Returned for modification 15 January
2001/Accepted 1 May 2001
Macrophages produce reactive oxygen species and reactive nitrogen
species that have potent antimicrobial activity. Resistance to killing
by macrophages is critical to the virulence of
Mycobacterium tuberculosis. M. tuberculosis has two
genes encoding superoxide dismutase proteins, sodA and
sodC. SodC is a Cu,Zn superoxide dismutase responsible
for only a minor portion of the superoxide dismutase activity of
M. tuberculosis. However, SodC has a lipoprotein binding
motif, which suggests that it may be anchored in the membrane to
protect M. tuberculosis from reactive oxygen
intermediates at the bacterial 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. In this report, we show that the
M. tuberculosis sodC mutant is readily killed by
superoxide generated externally, while the isogenic parental
M. tuberculosis is unaffected under these
conditions. Furthermore, the sodC mutant has enhanced
susceptibility to killing by gamma interferon (IFN-
)-activated murine peritoneal macrophages producing oxidative burst
products but is unaffected by macrophages not activated by
IFN-
or by macrophages from respiratory burst-deficient
mice. These observations establish that the Cu,Zn superoxide dismutase
contributes to the resistance of M. tuberculosis
against oxidative burst products generated by activated macrophages.
*
Corresponding author. Mailing address: University of
California, San Diego, 9500 Gilman Dr., La Jolla, CA 92093-0640. Phone: (858) 534-6024. Fax: (858) 534-6020. E-mail:
nbuchmeier{at}ucsd.edu.
Infection and Immunity, August 2001, p. 4980-4987, Vol. 69, No. 8
0019-9567/01/$04.00+0 DOI: 10.1128/IAI.69.8.4980-4987.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
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