Genetic and Redox Determinants of Nitric Oxide Cytotoxicity in a Salmonella Typhimurium Model

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1995 Jul 3

PMID 7604003

Citations 90

Authors

M A De Groote

D Granger

Y Xu

G Campbell

R Prince

F C Fang

Affiliations

Soon will be listed here.

Abstract

Paradoxically, nitric oxide (NO) has been found to exhibit cytotoxic, antiproliferative, or cytoprotective activity under different conditions. We have utilized Salmonella mutants deficient in antioxidant defenses or peptide transport to gain insights into NO actions. Comparison of three NO donor compounds reveals distinct and independent cellular responses associated with specific redox forms of NO. The peroxynitrite (OONO-) generator 3-morpholinosydnonimine hydrochloride mediates oxygen-dependent Salmonella killing, whereas S-nitrosoglutathione (GSNO) causes oxygen-independent cytostasis, and the NO. donor diethylenetriamine-nitric oxide adduct has no antibacterial activity. GSNO has the greatest activity for stationary cells, a characteristic relevant to latent or intracellular pathogens. Moreover, the cytostatic activity of GSNO may best correlate with antiproliferative or antimicrobial effects of NO, which are unassociated with overt cell injury. dpp mutants defective in active dipeptide transport are resistant to GSNO, implicating heterolytic NO+ transfer rather than homolytic NO. release in the mechanism of cytostasis. This transport system may provide a specific pathway for GSNO-mediated signaling in biological systems. The redox state and associated carrier molecules are critical determinants of NO activity.

Citing Articles

The human gut microbiome in health and disease: time for a new chapter?.

Lee J, Bays D, Savage H, Baumler A Infect Immun. 2024; 92(11):e0030224.

PMID: 39347570 PMC: 11556149. DOI: 10.1128/iai.00302-24.

Gut dysbiosis: Ecological causes and causative effects on human disease.

Winter S, Baumler A Proc Natl Acad Sci U S A. 2023; 120(50):e2316579120.

PMID: 38048456 PMC: 10722970. DOI: 10.1073/pnas.2316579120.

The Triple Crown: NO, CO, and HS in cancer cell biology.

Oza P, Kashfi K Pharmacol Ther. 2023; 249:108502.

PMID: 37517510 PMC: 10529678. DOI: 10.1016/j.pharmthera.2023.108502.

Nitric oxide is a host cue for Salmonella Typhimurium systemic infection in mice.

Jiang L, Li W, Hou X, Ma S, Wang X, Yan X Commun Biol. 2023; 6(1):501.

PMID: 37161082 PMC: 10169850. DOI: 10.1038/s42003-023-04876-1.

A Novel Approach to Vaccine Development: Concomitant Pathogen Inactivation and Host Immune Stimulation by Peroxynitrite.

Rotem S, Bar-Haim E, Elia U, Cohen H, Lazar S, Cohen O Vaccines (Basel). 2022; 10(10).

PMID: 36298458 PMC: 9607248. DOI: 10.3390/vaccines10101593.

References

Suzuki H, Kumagai H, Tochikura T . Isolation, genetic mapping, and characterization of Escherichia coli K-12 mutants lacking gamma-glutamyltranspeptidase. J Bacteriol. 1987; 169(9):3926-31. PMC: 213689. DOI: 10.1128/jb.169.9.3926-3931.1987. View

Higgins C, Hiles I, Salmond G, Gill D, Downie J, Evans I . A family of related ATP-binding subunits coupled to many distinct biological processes in bacteria. Nature. 1986; 323(6087):448-50. DOI: 10.1038/323448a0. View

Rayssiguier C, Thaler D, Radman M . The barrier to recombination between Escherichia coli and Salmonella typhimurium is disrupted in mismatch-repair mutants. Nature. 1989; 342(6248):396-401. DOI: 10.1038/342396a0. View

Radi R, Beckman J, Bush K, Freeman B . Peroxynitrite oxidation of sulfhydryls. The cytotoxic potential of superoxide and nitric oxide. J Biol Chem. 1991; 266(7):4244-50. View

Wink D, Kasprzak K, Maragos C, Elespuru R, Misra M, Dunams T . DNA deaminating ability and genotoxicity of nitric oxide and its progenitors. Science. 1991; 254(5034):1001-3. DOI: 10.1126/science.1948068. View

Abouhamad W, Manson M, Gibson M, Higgins C . Peptide transport and chemotaxis in Escherichia coli and Salmonella typhimurium: characterization of the dipeptide permease (Dpp) and the dipeptide-binding protein. Mol Microbiol. 1991; 5(5):1035-47. DOI: 10.1111/j.1365-2958.1991.tb01876.x. View

Stamler J, Simon D, Osborne J, Mullins M, Jaraki O, Michel T . S-nitrosylation of proteins with nitric oxide: synthesis and characterization of biologically active compounds. Proc Natl Acad Sci U S A. 1992; 89(1):444-8. PMC: 48254. DOI: 10.1073/pnas.89.1.444. View

Arroyo P, Mower H, Cooney R . Mutagenicity of nitric oxide and its inhibition by antioxidants. Mutat Res. 1992; 281(3):193-202. DOI: 10.1016/0165-7992(92)90008-6. View

Nathan C . Nitric oxide as a secretory product of mammalian cells. FASEB J. 1992; 6(12):3051-64. View

10.

Fang F, Libby S, Buchmeier N, Loewen P, Switala J, Harwood J . The alternative sigma factor katF (rpoS) regulates Salmonella virulence. Proc Natl Acad Sci U S A. 1992; 89(24):11978-82. PMC: 50681. DOI: 10.1073/pnas.89.24.11978. View

11.

Higgins C . ABC transporters: from microorganisms to man. Annu Rev Cell Biol. 1992; 8:67-113. DOI: 10.1146/annurev.cb.08.110192.000435. View

12.

Buchmeier N, Lipps C, So M, Heffron F . Recombination-deficient mutants of Salmonella typhimurium are avirulent and sensitive to the oxidative burst of macrophages. Mol Microbiol. 1993; 7(6):933-6. DOI: 10.1111/j.1365-2958.1993.tb01184.x. View

13.

Lipton S, Choi Y, Pan Z, Lei S, Chen H, Sucher N . A redox-based mechanism for the neuroprotective and neurodestructive effects of nitric oxide and related nitroso-compounds. Nature. 1993; 364(6438):626-32. DOI: 10.1038/364626a0. View

14.

Huie R, Padmaja S . The reaction of no with superoxide. Free Radic Res Commun. 1993; 18(4):195-9. DOI: 10.3109/10715769309145868. View

15.

Fierer J, Eckmann L, Fang F, Pfeifer C, Finlay B, Guiney D . Expression of the Salmonella virulence plasmid gene spvB in cultured macrophages and nonphagocytic cells. Infect Immun. 1993; 61(12):5231-6. PMC: 281306. DOI: 10.1128/iai.61.12.5231-5236.1993. View

16.

Choi D . Nitric oxide: foe or friend to the injured brain?. Proc Natl Acad Sci U S A. 1993; 90(21):9741-3. PMC: 47648. DOI: 10.1073/pnas.90.21.9741. View

17.

Nunoshiba T, Wishnok J, Tannenbaum S, 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; 90(21):9993-7. PMC: 47699. DOI: 10.1073/pnas.90.21.9993. View

18.

Gaston B, Reilly J, Drazen J, Fackler J, Ramdev P, Arnelle D . Endogenous nitrogen oxides and bronchodilator S-nitrosothiols in human airways. Proc Natl Acad Sci U S A. 1993; 90(23):10957-61. PMC: 47900. DOI: 10.1073/pnas.90.23.10957. View

19.

Prince R, Xu Y, Libby S, Fang F . Cloning and sequencing of the gene encoding the RpoS (KatF) sigma factor from Salmonella typhimurium 14028s. Biochim Biophys Acta. 1994; 1219(1):198-200. DOI: 10.1016/0167-4781(94)90271-2. View

20.

Stamler J . Redox signaling: nitrosylation and related target interactions of nitric oxide. Cell. 1994; 78(6):931-6. DOI: 10.1016/0092-8674(94)90269-0. View