Abstract
ABSTRACTMycobacterium tuberculosishas a relatively high resistance to killing by hydrogen peroxide and organic peroxides. Resistance may be mediated by mycobacterial catalase-peroxidase (KatG) and possibly by alkyl hydroperoxide reductase (AhpC). To determine the interrelationship between sensitivity to H2O2, catalase and peroxidase activities, and bacillary growth rates measured both intracellularly in human monocytes and in culture medium, we examined one laboratory strain, two clinical isolates, and three recombinant strains ofM. tuberculosiswith differing levels of KatG and AhpC. Five of the mycobacterial strains had intracellular doubling times of 27 to 32 h, while one KatG-deficient clinical isolate (ATCC 35825) doubled in ∼76 h. Killing of mycobacteria by exogenously added H2O2was more pronounced for intracellular bacilli than for those bacilli derived from disrupted monocytes. Strains with no detectable KatG expression or catalase activity were relatively sensitive to killing (43 to 67% killing) by exogenous H2O2. However, once even minimal catalase activity was present, mycobacterial catalase activity over a 10-fold range (0.56 to 6.2 U/mg) was associated with survival of 85% of the bacilli. Peroxidase activity levels correlated significantly with resistance of the mycobacterial strains to H2O2-mediated killing. An endogenous oxidative burst induction by 4β-phorbol 12β-myristate 13α-acetate treatment of infected monocytes reduced the viability of the KatG null strain (H37Rv Inhr) but not the KatG-overexpressing strain [H37Rv(pMH59)]. These results suggest that mycobacterial resistance to oxidative metabolites (including H2O2and other peroxides) may be an important mechanism of bacillary survival within the host phagocyte.
References
41
Referenced
213
10.1016/S0006-2952(97)00163-9
10.1016/S1368-7646(98)80028-9
10.1016/S0021-9258(19)50881-X
10.1016/S0021-9258(18)47038-X
10.1084/jem.175.4.1111
10.1084/jem.181.1.257
-
Deng W. Thiel B. Tannenbaum C. S. Hamilton T. A. Stuehr D. J. Synergistic cooperation between T cell lymphokines for induction of the nitric oxide synthase gene in murine peritoneal macrophages.J. Immunol.1511993322329
(
10.4049/jimmunol.151.1.322
) / J. Immunol. / Synergistic cooperation between T cell lymphokines for induction of the nitric oxide synthase gene in murine peritoneal macrophages by Deng W. (1993) 10.1016/0008-8749(91)90014-3
10.1152/jappl.1986.60.2.353
10.1074/jbc.270.45.27292
10.1128/iai.62.10.4650-4651.1994
10.1016/S0140-6736(52)92110-7
10.1128/jb.175.13.4255-4259.1993
10.1128/iai.65.4.1395-1401.1997
10.1099/00221287-104-1-37
10.1099/00221287-107-2-273
10.1074/jbc.272.5.2834
10.1056/NEJM199612263352604
10.1172/JCI119810
10.1128/iai.64.2.452-459.1996
10.1128/iai.65.11.4850-4857.1997
10.1002/jcb.240220306
10.1093/oxfordjournals.bmb.a072272
10.1016/S0021-9258(19)52451-6
10.1046/j.1365-2958.1998.00774.x
10.1002/path.1700860213
10.1084/jem.177.6.1691
10.1084/jem.180.4.1499
- Morse W. C. Weiser O. L. Kuhns D. M. Fusillo M. Dail M. C. Evans J. R. Study of the virulence of isoniazid-resistant tubercle bacilli in guinea pigs and mice.Am. Rev. Tuberc.691954464468 / Am. Rev. Tuberc. / Study of the virulence of isoniazid-resistant tubercle bacilli in guinea pigs and mice by Morse W. C. (1954)
10.1084/jem.158.3.670
10.1016/0882-4010(91)90054-E
-
Russell D. G. Dant J. Sturgill-Koszycki S. Mycobacterium avium- and Mycobacterium tuberculosis-containing vacuoles are dynamic, fusion-competent vesicles that are accessible to glycosphingolipids from the host cell plasmalemma.J. Immunol.156199647644773
(
10.4049/jimmunol.156.12.4764
) / J. Immunol. / Mycobacterium avium- and Mycobacterium tuberculosis-containing vacuoles are dynamic, fusion-competent vesicles that are accessible to glycosphingolipids from the host cell plasmalemma by Russell D. G. (1996) 10.1098/rstb.1997.0114
10.1128/iai.64.8.3224-3230.1996
- Scoazec J. Y. Fischer A. Nezelof C. Les infections generalisees a BCG, expression d’un deficit multi-factoriel de la bactericidie intramacrophagique. Etude anatomo-clinique de 11 cas.Arch. Fr. Pediatr.411984681687 / Arch. Fr. Pediatr. / Les infections generalisees a BCG, expression d’un deficit multi-factoriel de la bactericidie intramacrophagique. Etude anatomo-clinique de 11 cas by Scoazec J. Y. (1984)
10.1126/science.272.5268.1641
10.1002/j.1460-2075.1996.tb01088.x
10.1128/iai.65.7.2537-2541.1997
10.1111/j.1365-2958.1995.tb02276.x
-
Xu S. Cooper A. Sturgill-Koszycki S. van Heyningen T. Chatterjee D. Orme I. Allen P. Russell D. G. Intracellular trafficking in Mycobacterium tuberculosis and Mycobacterium avium-infected macrophages.J. Immunol.153199425682578
(
10.4049/jimmunol.153.6.2568
) / J. Immunol. / Intracellular trafficking in Mycobacterium tuberculosis and Mycobacterium avium-infected macrophages by Xu S. (1994) 10.1038/358591a0
Dates
Type | When |
---|---|
Created | 5 years, 8 months ago (Dec. 31, 2019, 10:29 a.m.) |
Deposited | 1 year, 11 months ago (Sept. 24, 2023, 10:36 a.m.) |
Indexed | 1 month ago (Aug. 2, 2025, 12:48 a.m.) |
Issued | 26 years, 8 months ago (Jan. 1, 1999) |
Published | 26 years, 8 months ago (Jan. 1, 1999) |
Published Print | 26 years, 8 months ago (Jan. 1, 1999) |
@article{Manca_1999, title={Mycobacterium tuberculosisCatalase and Peroxidase Activities and Resistance to Oxidative Killing in Human Monocytes In Vitro}, volume={67}, ISSN={1098-5522}, url={http://dx.doi.org/10.1128/iai.67.1.74-79.1999}, DOI={10.1128/iai.67.1.74-79.1999}, number={1}, journal={Infection and Immunity}, publisher={American Society for Microbiology}, author={Manca, Claudia and Paul, Simon and Barry, Clifton E. and Freedman, Victoria H. and Kaplan, Gilla}, editor={Sansonetti, P. J.}, year={1999}, month=jan, pages={74–79} }