Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1997 Jun 15;99(12):2818–2825. doi: 10.1172/JCI119473

Perspectives series: host/pathogen interactions. Mechanisms of nitric oxide-related antimicrobial activity.

F C Fang 1
PMCID: PMC508130  PMID: 9185502

Full Text

The Full Text of this article is available as a PDF (155.0 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abouhamad W. N., Manson M., Gibson M. M., Higgins C. F. Peptide transport and chemotaxis in Escherichia coli and Salmonella typhimurium: characterization of the dipeptide permease (Dpp) and the dipeptide-binding protein. Mol Microbiol. 1991 May;5(5):1035–1047. doi: 10.1111/j.1365-2958.1991.tb01876.x. [DOI] [PubMed] [Google Scholar]
  2. Adams L. B., Hibbs J. B., Jr, Taintor R. R., Krahenbuhl J. L. Microbiostatic effect of murine-activated macrophages for Toxoplasma gondii. Role for synthesis of inorganic nitrogen oxides from L-arginine. J Immunol. 1990 Apr 1;144(7):2725–2729. [PubMed] [Google Scholar]
  3. Ahmed S. F., Oswald I. P., Caspar P., Hieny S., Keefer L., Sher A., James S. L. Developmental differences determine larval susceptibility to nitric oxide-mediated killing in a murine model of vaccination against Schistosoma mansoni. Infect Immun. 1997 Jan;65(1):219–226. doi: 10.1128/iai.65.1.219-226.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Anstey N. M., Weinberg J. B., Hassanali M. Y., Mwaikambo E. D., Manyenga D., Misukonis M. A., Arnelle D. R., Hollis D., McDonald M. I., Granger D. L. Nitric oxide in Tanzanian children with malaria: inverse relationship between malaria severity and nitric oxide production/nitric oxide synthase type 2 expression. J Exp Med. 1996 Aug 1;184(2):557–567. doi: 10.1084/jem.184.2.557. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Assreuy J., Cunha F. Q., Epperlein M., Noronha-Dutra A., O'Donnell C. A., Liew F. Y., Moncada S. Production of nitric oxide and superoxide by activated macrophages and killing of Leishmania major. Eur J Immunol. 1994 Mar;24(3):672–676. doi: 10.1002/eji.1830240328. [DOI] [PubMed] [Google Scholar]
  6. Buchmeier N. A., Lipps C. J., So M. Y., Heffron F. Recombination-deficient mutants of Salmonella typhimurium are avirulent and sensitive to the oxidative burst of macrophages. Mol Microbiol. 1993 Mar;7(6):933–936. doi: 10.1111/j.1365-2958.1993.tb01184.x. [DOI] [PubMed] [Google Scholar]
  7. Bukrinsky M. I., Nottet H. S., Schmidtmayerova H., Dubrovsky L., Flanagan C. R., Mullins M. E., Lipton S. A., Gendelman H. E. Regulation of nitric oxide synthase activity in human immunodeficiency virus type 1 (HIV-1)-infected monocytes: implications for HIV-associated neurological disease. J Exp Med. 1995 Feb 1;181(2):735–745. doi: 10.1084/jem.181.2.735. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Christman M. F., Morgan R. W., Jacobson F. S., Ames B. N. Positive control of a regulon for defenses against oxidative stress and some heat-shock proteins in Salmonella typhimurium. Cell. 1985 Jul;41(3):753–762. doi: 10.1016/s0092-8674(85)80056-8. [DOI] [PubMed] [Google Scholar]
  9. Condino-Neto A., Muscará M. N., Grumach A. S., Carneiro-Sampaio M. M., De Nucci G. Neutrophils and mononuclear cells from patients with chronic granulomatous disease release nitric oxide. Br J Clin Pharmacol. 1993 May;35(5):485–490. doi: 10.1111/j.1365-2125.1993.tb04174.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Cowley S. C., Myltseva S. V., Nano F. E. Phase variation in Francisella tularensis affecting intracellular growth, lipopolysaccharide antigenicity and nitric oxide production. Mol Microbiol. 1996 May;20(4):867–874. doi: 10.1111/j.1365-2958.1996.tb02524.x. [DOI] [PubMed] [Google Scholar]
  11. Crow J. P., Beckman J. S. Reactions between nitric oxide, superoxide, and peroxynitrite: footprints of peroxynitrite in vivo. Adv Pharmacol. 1995;34:17–43. doi: 10.1016/s1054-3589(08)61079-0. [DOI] [PubMed] [Google Scholar]
  12. De Groote M. A., Fang F. C. NO inhibitions: antimicrobial properties of nitric oxide. Clin Infect Dis. 1995 Oct;21 (Suppl 2):S162–S165. doi: 10.1093/clinids/21.supplement_2.s162. [DOI] [PubMed] [Google Scholar]
  13. De Groote M. A., Granger D., Xu Y., Campbell G., Prince R., Fang F. C. Genetic and redox determinants of nitric oxide cytotoxicity in a Salmonella typhimurium model. Proc Natl Acad Sci U S A. 1995 Jul 3;92(14):6399–6403. doi: 10.1073/pnas.92.14.6399. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. De Groote M. A., Testerman T., Xu Y., Stauffer G., Fang F. C. Homocysteine antagonism of nitric oxide-related cytostasis in Salmonella typhimurium. Science. 1996 Apr 19;272(5260):414–417. doi: 10.1126/science.272.5260.414. [DOI] [PubMed] [Google Scholar]
  15. De Maria R., Cifone M. G., Trotta R., Rippo M. R., Festuccia C., Santoni A., Testi R. Triggering of human monocyte activation through CD69, a member of the natural killer cell gene complex family of signal transducing receptors. J Exp Med. 1994 Nov 1;180(5):1999–2004. doi: 10.1084/jem.180.5.1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Denicola A., Souza J. M., Radi R., Lissi E. Nitric oxide diffusion in membranes determined by fluorescence quenching. Arch Biochem Biophys. 1996 Apr 1;328(1):208–212. doi: 10.1006/abbi.1996.0162. [DOI] [PubMed] [Google Scholar]
  17. Drapier J. C., Pellat C., Henry Y. Generation of EPR-detectable nitrosyl-iron complexes in tumor target cells cocultured with activated macrophages. J Biol Chem. 1991 Jun 5;266(16):10162–10167. [PubMed] [Google Scholar]
  18. Eiserich J. P., Cross C. E., Jones A. D., Halliwell B., van der Vliet A. Formation of nitrating and chlorinating species by reaction of nitrite with hypochlorous acid. A novel mechanism for nitric oxide-mediated protein modification. J Biol Chem. 1996 Aug 9;271(32):19199–19208. doi: 10.1074/jbc.271.32.19199. [DOI] [PubMed] [Google Scholar]
  19. Evans T. G., Thai L., Granger D. L., Hibbs J. B., Jr Effect of in vivo inhibition of nitric oxide production in murine leishmaniasis. J Immunol. 1993 Jul 15;151(2):907–915. [PubMed] [Google Scholar]
  20. Evans T. J., Buttery L. D., Carpenter A., Springall D. R., Polak J. M., Cohen J. Cytokine-treated human neutrophils contain inducible nitric oxide synthase that produces nitration of ingested bacteria. Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9553–9558. doi: 10.1073/pnas.93.18.9553. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Fairlamb A. H., Cerami A. Metabolism and functions of trypanothione in the Kinetoplastida. Annu Rev Microbiol. 1992;46:695–729. doi: 10.1146/annurev.mi.46.100192.003403. [DOI] [PubMed] [Google Scholar]
  22. Fernandes P. D., Assreuy J. Role of nitric oxide and superoxide in Giardia lamblia killing. Braz J Med Biol Res. 1997 Jan;30(1):93–99. doi: 10.1590/s0100-879x1997000100015. [DOI] [PubMed] [Google Scholar]
  23. Freeman B. A., White C. R., Gutierrez H., Paler-Martínez A., Tarpey M. M., Rubbo H. Oxygen radical-nitric oxide reactions in vascular diseases. Adv Pharmacol. 1995;34:45–69. doi: 10.1016/s1054-3589(08)61080-7. [DOI] [PubMed] [Google Scholar]
  24. Gow A. J., Buerk D. G., Ischiropoulos H. A novel reaction mechanism for the formation of S-nitrosothiol in vivo. J Biol Chem. 1997 Jan 31;272(5):2841–2845. doi: 10.1074/jbc.272.5.2841. [DOI] [PubMed] [Google Scholar]
  25. Halliwell B., Hu M. L., Louie S., Duvall T. R., Tarkington B. K., Motchnik P., Cross C. E. Interaction of nitrogen dioxide with human plasma. Antioxidant depletion and oxidative damage. FEBS Lett. 1992 Nov 16;313(1):62–66. doi: 10.1016/0014-5793(92)81185-o. [DOI] [PubMed] [Google Scholar]
  26. Hausladen A., Fridovich I. Superoxide and peroxynitrite inactivate aconitases, but nitric oxide does not. J Biol Chem. 1994 Nov 25;269(47):29405–29408. [PubMed] [Google Scholar]
  27. Hausladen A., Privalle C. T., Keng T., DeAngelo J., Stamler J. S. Nitrosative stress: activation of the transcription factor OxyR. Cell. 1996 Sep 6;86(5):719–729. doi: 10.1016/s0092-8674(00)80147-6. [DOI] [PubMed] [Google Scholar]
  28. Hentze M. W., Kühn L. C. Molecular control of vertebrate iron metabolism: mRNA-based regulatory circuits operated by iron, nitric oxide, and oxidative stress. Proc Natl Acad Sci U S A. 1996 Aug 6;93(16):8175–8182. doi: 10.1073/pnas.93.16.8175. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Hibbs J. B., Jr, Westenfelder C., Taintor R., Vavrin Z., Kablitz C., Baranowski R. L., Ward J. H., Menlove R. L., McMurry M. P., Kushner J. P. Evidence for cytokine-inducible nitric oxide synthesis from L-arginine in patients receiving interleukin-2 therapy. J Clin Invest. 1992 Mar;89(3):867–877. doi: 10.1172/JCI115666. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Ischiropoulos H., al-Mehdi A. B. Peroxynitrite-mediated oxidative protein modifications. FEBS Lett. 1995 May 15;364(3):279–282. doi: 10.1016/0014-5793(95)00307-u. [DOI] [PubMed] [Google Scholar]
  31. Juedes M. J., Wogan G. N. Peroxynitrite-induced mutation spectra of pSP189 following replication in bacteria and in human cells. Mutat Res. 1996 Jan 17;349(1):51–61. doi: 10.1016/0027-5107(95)00152-2. [DOI] [PubMed] [Google Scholar]
  32. Kanner J., Harel S., Granit R. Nitric oxide as an antioxidant. Arch Biochem Biophys. 1991 Aug 15;289(1):130–136. doi: 10.1016/0003-9861(91)90452-o. [DOI] [PubMed] [Google Scholar]
  33. Kaplan S. S., Lancaster J. R., Jr, Basford R. E., Simmons R. L. Effect of nitric oxide on staphylococcal killing and interactive effect with superoxide. Infect Immun. 1996 Jan;64(1):69–76. doi: 10.1128/iai.64.1.69-76.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Karupiah G., Harris N. Inhibition of viral replication by nitric oxide and its reversal by ferrous sulfate and tricarboxylic acid cycle metabolites. J Exp Med. 1995 Jun 1;181(6):2171–2179. doi: 10.1084/jem.181.6.2171. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Kim Y. M., Bergonia H. A., Müller C., Pitt B. R., Watkins W. D., Lancaster J. R., Jr Nitric oxide and intracellular heme. Adv Pharmacol. 1995;34:277–291. doi: 10.1016/s1054-3589(08)61092-3. [DOI] [PubMed] [Google Scholar]
  36. Kim Y. M., Bergonia H., Lancaster J. R., Jr Nitrogen oxide-induced autoprotection in isolated rat hepatocytes. FEBS Lett. 1995 Oct 30;374(2):228–232. doi: 10.1016/0014-5793(95)01115-u. [DOI] [PubMed] [Google Scholar]
  37. Kumar V., Jindal S. K., Ganguly N. K. Release of reactive oxygen and nitrogen intermediates from monocytes of patients with pulmonary tuberculosis. Scand J Clin Lab Invest. 1995 Apr;55(2):163–169. doi: 10.3109/00365519509089609. [DOI] [PubMed] [Google Scholar]
  38. Lepoivre M., Chenais B., Yapo A., Lemaire G., Thelander L., Tenu J. P. Alterations of ribonucleotide reductase activity following induction of the nitrite-generating pathway in adenocarcinoma cells. J Biol Chem. 1990 Aug 25;265(24):14143–14149. [PubMed] [Google Scholar]
  39. Loscalzo J. The oxidant stress of hyperhomocyst(e)inemia. J Clin Invest. 1996 Jul 1;98(1):5–7. doi: 10.1172/JCI118776. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. MacMicking J. D., North R. J., LaCourse R., Mudgett J. S., Shah S. K., Nathan C. F. Identification of nitric oxide synthase as a protective locus against tuberculosis. Proc Natl Acad Sci U S A. 1997 May 13;94(10):5243–5248. doi: 10.1073/pnas.94.10.5243. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Mannick J. B., Asano K., Izumi K., Kieff E., Stamler J. S. Nitric oxide produced by human B lymphocytes inhibits apoptosis and Epstein-Barr virus reactivation. Cell. 1994 Dec 30;79(7):1137–1146. doi: 10.1016/0092-8674(94)90005-1. [DOI] [PubMed] [Google Scholar]
  42. Maragos C. M., Andrews A. W., Keefer L. K., Elespuru R. K. Mutagenicity of glyceryl trinitrate (nitroglycerin) in Salmonella typhimurium. Mutat Res. 1993 Jan;298(3):187–195. doi: 10.1016/0165-1218(93)90040-k. [DOI] [PubMed] [Google Scholar]
  43. Melková Z., Esteban M. Inhibition of vaccinia virus DNA replication by inducible expression of nitric oxide synthase. J Immunol. 1995 Dec 15;155(12):5711–5718. [PubMed] [Google Scholar]
  44. Morris S. L., Hansen J. N. Inhibition of Bacillus cereus spore outgrowth by covalent modification of a sulfhydryl group by nitrosothiol and iodoacetate. J Bacteriol. 1981 Nov;148(2):465–471. doi: 10.1128/jb.148.2.465-471.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Murad F. Regulation of cytosolic guanylyl cyclase by nitric oxide: the NO-cyclic GMP signal transduction system. Adv Pharmacol. 1994;26:19–33. doi: 10.1016/s1054-3589(08)60049-6. [DOI] [PubMed] [Google Scholar]
  46. Newton G. L., Arnold K., Price M. S., Sherrill C., Delcardayre S. B., Aharonowitz Y., Cohen G., Davies J., Fahey R. C., Davis C. Distribution of thiols in microorganisms: mycothiol is a major thiol in most actinomycetes. J Bacteriol. 1996 Apr;178(7):1990–1995. doi: 10.1128/jb.178.7.1990-1995.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Nicholson S., Bonecini-Almeida M. da G., Lapa e Silva J. R., Nathan C., Xie Q. W., Mumford R., Weidner J. R., Calaycay J., Geng J., Boechat N. Inducible nitric oxide synthase in pulmonary alveolar macrophages from patients with tuberculosis. J Exp Med. 1996 May 1;183(5):2293–2302. doi: 10.1084/jem.183.5.2293. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Noronha-Dutra A. A., Epperlein M. M., Woolf N. Reaction of nitric oxide with hydrogen peroxide to produce potentially cytotoxic singlet oxygen as a model for nitric oxide-mediated killing. FEBS Lett. 1993 Apr 19;321(1):59–62. doi: 10.1016/0014-5793(93)80621-z. [DOI] [PubMed] [Google Scholar]
  49. Nunoshiba T., DeRojas-Walker T., Tannenbaum S. R., Demple B. Roles of nitric oxide in inducible resistance of Escherichia coli to activated murine macrophages. Infect Immun. 1995 Mar;63(3):794–798. doi: 10.1128/iai.63.3.794-798.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Nunoshiba T., deRojas-Walker T., Wishnok J. S., Tannenbaum S. R., Demple B. Activation by nitric oxide of an oxidative-stress response that defends Escherichia coli against activated macrophages. Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):9993–9997. doi: 10.1073/pnas.90.21.9993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Ochoa J. B., Udekwu A. O., Billiar T. R., Curran R. D., Cerra F. B., Simmons R. L., Peitzman A. B. Nitrogen oxide levels in patients after trauma and during sepsis. Ann Surg. 1991 Nov;214(5):621–626. doi: 10.1097/00000658-199111000-00013. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Pacelli R., Wink D. A., Cook J. A., Krishna M. C., DeGraff W., Friedman N., Tsokos M., Samuni A., Mitchell J. B. Nitric oxide potentiates hydrogen peroxide-induced killing of Escherichia coli. J Exp Med. 1995 Nov 1;182(5):1469–1479. doi: 10.1084/jem.182.5.1469. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Park J. W. Attenuation of p47phox and p67phox membrane translocation as the inhibitory mechanism of S-nitrosothiol on the respiratory burst oxidase in human neutrophils. Biochem Biophys Res Commun. 1996 Mar 7;220(1):31–35. doi: 10.1006/bbrc.1996.0351. [DOI] [PubMed] [Google Scholar]
  54. Prada J., Malinowski J., Muller S., Bienzle U., Kremsner P. G. Effects of Plasmodium vinckei hemozoin on the production of oxygen radicals and nitrogen oxides in murine macrophages. Am J Trop Med Hyg. 1996 Jun;54(6):620–624. doi: 10.4269/ajtmh.1996.54.620. [DOI] [PubMed] [Google Scholar]
  55. Rubbo H., Radi R., Trujillo M., Telleri R., Kalyanaraman B., Barnes S., Kirk M., Freeman B. A. Nitric oxide regulation of superoxide and peroxynitrite-dependent lipid peroxidation. Formation of novel nitrogen-containing oxidized lipid derivatives. J Biol Chem. 1994 Oct 21;269(42):26066–26075. [PubMed] [Google Scholar]
  56. Singh S. P., Wishnok J. S., Keshive M., Deen W. M., Tannenbaum S. R. The chemistry of the S-nitrosoglutathione/glutathione system. Proc Natl Acad Sci U S A. 1996 Dec 10;93(25):14428–14433. doi: 10.1073/pnas.93.25.14428. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. St Clair E. W., Wilkinson W. E., Lang T., Sanders L., Misukonis M. A., Gilkeson G. S., Pisetsky D. S., Granger D. I., Weinberg J. B. Increased expression of blood mononuclear cell nitric oxide synthase type 2 in rheumatoid arthritis patients. J Exp Med. 1996 Sep 1;184(3):1173–1178. doi: 10.1084/jem.184.3.1173. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Stamler J. S. S-nitrosothiols and the bioregulatory actions of nitrogen oxides through reactions with thiol groups. Curr Top Microbiol Immunol. 1995;196:19–36. doi: 10.1007/978-3-642-79130-7_4. [DOI] [PubMed] [Google Scholar]
  59. Stenger S., Donhauser N., Thüring H., Röllinghoff M., Bogdan C. Reactivation of latent leishmaniasis by inhibition of inducible nitric oxide synthase. J Exp Med. 1996 Apr 1;183(4):1501–1514. doi: 10.1084/jem.183.4.1501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Sternberg J., Mabbott N., Sutherland I., Liew F. Y. Inhibition of nitric oxide synthesis leads to reduced parasitemia in murine Trypanosoma brucei infection. Infect Immun. 1994 May;62(5):2135–2137. doi: 10.1128/iai.62.5.2135-2137.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Tsaneva I. R., Weiss B. soxR, a locus governing a superoxide response regulon in Escherichia coli K-12. J Bacteriol. 1990 Aug;172(8):4197–4205. doi: 10.1128/jb.172.8.4197-4205.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Vazquez-Torres A., Jones-Carson J., Balish E. Peroxynitrite contributes to the candidacidal activity of nitric oxide-producing macrophages. Infect Immun. 1996 Aug;64(8):3127–3133. doi: 10.1128/iai.64.8.3127-3133.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Vouldoukis I., Riveros-Moreno V., Dugas B., Ouaaz F., Bécherel P., Debré P., Moncada S., Mossalayi M. D. The killing of Leishmania major by human macrophages is mediated by nitric oxide induced after ligation of the Fc epsilon RII/CD23 surface antigen. Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):7804–7808. doi: 10.1073/pnas.92.17.7804. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Warren J. B., Loi R., Rendell N. B., Taylor G. W. Nitric oxide is inactivated by the bacterial pigment pyocyanin. Biochem J. 1990 Mar 15;266(3):921–923. [PMC free article] [PubMed] [Google Scholar]
  65. Wei X. Q., Charles I. G., Smith A., Ure J., Feng G. J., Huang F. P., Xu D., Muller W., Moncada S., Liew F. Y. Altered immune responses in mice lacking inducible nitric oxide synthase. Nature. 1995 Jun 1;375(6530):408–411. doi: 10.1038/375408a0. [DOI] [PubMed] [Google Scholar]
  66. Wheeler M. A., Smith S. D., García-Cardeña G., Nathan C. F., Weiss R. M., Sessa W. C. Bacterial infection induces nitric oxide synthase in human neutrophils. J Clin Invest. 1997 Jan 1;99(1):110–116. doi: 10.1172/JCI119121. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Wink D. A., Cook J. A., Pacelli R., Liebmann J., Krishna M. C., Mitchell J. B. Nitric oxide (NO) protects against cellular damage by reactive oxygen species. Toxicol Lett. 1995 Dec;82-83:221–226. doi: 10.1016/0378-4274(95)03557-5. [DOI] [PubMed] [Google Scholar]
  68. Wink D. A., Kasprzak K. S., Maragos C. M., Elespuru R. K., Misra M., Dunams T. M., Cebula T. A., Koch W. H., Andrews A. W., Allen J. S. DNA deaminating ability and genotoxicity of nitric oxide and its progenitors. Science. 1991 Nov 15;254(5034):1001–1003. doi: 10.1126/science.1948068. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES