TY - JOUR
T1 - Toxicity of nitrogen oxides and related oxidants on mycobacteria
T2 - M. tuberculosis is resistant to peroxynitrite anion
AU - Yu, K.
AU - Mitchell, C.
AU - Xing, Y.
AU - Magliozzo, R. S.
AU - Bloom, B. R.
AU - Chan, J.
N1 - Funding Information:
This work was supported in part by the New Jersey Foundation, the Heiser Foundation, and the Howard Hughes Medical Institute. We thank the machinists Tony Leggradro, Edward Schwartz, and Lester Arnholdt of the Albert Einstein College of Medicine Machine Shop and Henry Keller of County Welding (White Plains, New York) for the construction of Calypso and the acrylic quench-flow reactor.
PY - 1999/8
Y1 - 1999/8
N2 - Objective: To test the toxicity of reactive nitrogen intermediates (RNI), including authentic nitric oxide (NO), nitrogen dioxide (NO2), and peroxynitrite anion (ONOO-), a potent oxidant derived from NO and superoxide anion, on various mycobacterial strains including M. tuberculosis. Design: Relatively avirulent mycobacteria including M. smegmatis and BCG, as well as the pathogenic M. Bovis Ravenel and M. tuberculosis Erdman and the clinical isolate M160 (also known as the C strain) were tested for their susceptibility to the toxic effects of NO, NO2, and ONOO-. Deaerated, NO-saturated solutions as well as an anaerobic in vitro system in which mycobacteria can be exposed to desired concentrations of authentic NO or NO2, were employed in these studies. An in vitro ONOO- killing assay was used to examine the adverse effects of this NO-derived oxidant on the various strains of mycobacteria. Results: Both NO and NO2 exhibit antimycobacterial activity, with the former being more potent. Results obtained using ONOO- killing assay revealed that while avirulent mycobacteria including BCG and M. smegmatis are susceptible to this NO-derived oxidant, the virulent Erdman strain of M. tuberculosis and M. bovis, as well as the clinical tuberculous isolate M160, are remarkably resistant. Conclusion: These results suggest that the interactions between RNI and various species of mycobactiera could be highly specific. And since activated macrophages produce peroxynitrite, the significance of the ONOO- resistance of M. tuberculosis strains in relation to intracellular survival deserves further investigation.
AB - Objective: To test the toxicity of reactive nitrogen intermediates (RNI), including authentic nitric oxide (NO), nitrogen dioxide (NO2), and peroxynitrite anion (ONOO-), a potent oxidant derived from NO and superoxide anion, on various mycobacterial strains including M. tuberculosis. Design: Relatively avirulent mycobacteria including M. smegmatis and BCG, as well as the pathogenic M. Bovis Ravenel and M. tuberculosis Erdman and the clinical isolate M160 (also known as the C strain) were tested for their susceptibility to the toxic effects of NO, NO2, and ONOO-. Deaerated, NO-saturated solutions as well as an anaerobic in vitro system in which mycobacteria can be exposed to desired concentrations of authentic NO or NO2, were employed in these studies. An in vitro ONOO- killing assay was used to examine the adverse effects of this NO-derived oxidant on the various strains of mycobacteria. Results: Both NO and NO2 exhibit antimycobacterial activity, with the former being more potent. Results obtained using ONOO- killing assay revealed that while avirulent mycobacteria including BCG and M. smegmatis are susceptible to this NO-derived oxidant, the virulent Erdman strain of M. tuberculosis and M. bovis, as well as the clinical tuberculous isolate M160, are remarkably resistant. Conclusion: These results suggest that the interactions between RNI and various species of mycobactiera could be highly specific. And since activated macrophages produce peroxynitrite, the significance of the ONOO- resistance of M. tuberculosis strains in relation to intracellular survival deserves further investigation.
UR - http://www.scopus.com/inward/record.url?scp=0032830066&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032830066&partnerID=8YFLogxK
U2 - 10.1054/tuld.1998.0203
DO - 10.1054/tuld.1998.0203
M3 - Article
C2 - 10692986
AN - SCOPUS:0032830066
SN - 0962-8479
VL - 79
SP - 191
EP - 198
JO - Tubercle and Lung Disease
JF - Tubercle and Lung Disease
IS - 4
ER -
