Abstract
The respiratory burst of neutrophils is believed to kill bacteria by generating oxidative species, such as superoxide anion, hydrogen peroxide, and oxidized halogen species. The oxyR gene of Salmonella typhimurium controls a regulon induced by oxidative stress, such as exposure to hydrogen peroxide. Some researchers have suggested that oxyR may play a key role in bacterial survival following phagocytosis. We have tested this possibility by comparing the survival, following exposure to human neutrophils, of isogenic strains bearing different oxyR alleles. Neither inactivation of the oxyR gene nor constitutive overexpression of the oxyR-regulated proteins (oxyR1 allele) greatly alters bacterial resistance to neutrophils. The katG gene, encoding the oxyR-regulated enzyme hydroperoxidase I, was also without effect on survival following exposure to neutrophils. We conclude that the oxyR response does not play a significant role in the resistance of S. typhimurium to phagocytic killing in vitro.
Full text
PDF![2662](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4054/302866/a6a86c5723a7/iai00007-0020.png)
![2663](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4054/302866/ae1ec21b10ad/iai00007-0021.png)
![2664](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4054/302866/252462e4c8a2/iai00007-0022.png)
![2665](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4054/302866/faa42f40572a/iai00007-0023.png)
![2666](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4054/302866/ff7b49934dfa/iai00007-0024.png)
![2667](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4054/302866/123b24154d1e/iai00007-0025.png)
![2668](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4054/302866/dcff329717e8/iai00007-0026.png)
Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Barak M., Ulitzur S., Merzbach D. Phagocytosis-induced mutagenesis in bacteria. Mutat Res. 1983 Jul;121(1):7–16. doi: 10.1016/0165-7992(83)90080-5. [DOI] [PubMed] [Google Scholar]
- Beaman B. L., Black C. M., Doughty F., Beaman L. Role of superoxide dismutase and catalase as determinants of pathogenicity of Nocardia asteroides: importance in resistance to microbicidal activities of human polymorphonuclear neutrophils. Infect Immun. 1985 Jan;47(1):135–141. doi: 10.1128/iai.47.1.135-141.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Beaman L., Beaman B. L. Monoclonal antibodies demonstrate that superoxide dismutase contributes to protection of Nocardia asteroides within the intact host. Infect Immun. 1990 Sep;58(9):3122–3128. doi: 10.1128/iai.58.9.3122-3128.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bloch C. A., Ausubel F. M. Paraquat-mediated selection for mutations in the manganese-superoxide dismutase gene sodA. J Bacteriol. 1986 Nov;168(2):795–798. doi: 10.1128/jb.168.2.795-798.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Chan E., Weiss B. Endonuclease IV of Escherichia coli is induced by paraquat. Proc Natl Acad Sci U S A. 1987 May;84(10):3189–3193. doi: 10.1073/pnas.84.10.3189. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Cohen M. S., Britigan B. E., Hassett D. J., Rosen G. M. Do humans neutrophils form hydroxyl radical? Evaluation of an unresolved controversy. Free Radic Biol Med. 1988;5(2):81–88. doi: 10.1016/0891-5849(88)90033-0. [DOI] [PubMed] [Google Scholar]
- DeBruin L. S., Josephy P. D. Dichlorobenzidine-DNA binding catalyzed by peroxidative activation in Salmonella typhimurium. Arch Biochem Biophys. 1989 Feb 15;269(1):25–31. doi: 10.1016/0003-9861(89)90083-0. [DOI] [PubMed] [Google Scholar]
- Demple B., Halbrook J. Inducible repair of oxidative DNA damage in Escherichia coli. Nature. 1983 Aug 4;304(5925):466–468. doi: 10.1038/304466a0. [DOI] [PubMed] [Google Scholar]
- Demple B., Halbrook J., Linn S. Escherichia coli xth mutants are hypersensitive to hydrogen peroxide. J Bacteriol. 1983 Feb;153(2):1079–1082. doi: 10.1128/jb.153.2.1079-1082.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Eisenhauer P. B., Lehrer R. I. Mouse neutrophils lack defensins. Infect Immun. 1992 Aug;60(8):3446–3447. doi: 10.1128/iai.60.8.3446-3447.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Farr S. B., Kogoma T. Oxidative stress responses in Escherichia coli and Salmonella typhimurium. Microbiol Rev. 1991 Dec;55(4):561–585. doi: 10.1128/mr.55.4.561-585.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Farr S. B., Touati D., Kogoma T. Effects of oxygen stress on membrane functions in Escherichia coli: role of HPI catalase. J Bacteriol. 1988 Apr;170(4):1837–1842. doi: 10.1128/jb.170.4.1837-1842.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fields P. I., Groisman E. A., Heffron F. A Salmonella locus that controls resistance to microbicidal proteins from phagocytic cells. Science. 1989 Feb 24;243(4894 Pt 1):1059–1062. doi: 10.1126/science.2646710. [DOI] [PubMed] [Google Scholar]
- Fulton A. M., Loveless S. E., Heppner G. H. Mutagenic activity of tumor-associated macrophages in Salmonella typhimurium strains TA98 and TA 100. Cancer Res. 1984 Oct;44(10):4308–4311. [PubMed] [Google Scholar]
- Ganz T., Selsted M. E., Szklarek D., Harwig S. S., Daher K., Bainton D. F., Lehrer R. I. Defensins. Natural peptide antibiotics of human neutrophils. J Clin Invest. 1985 Oct;76(4):1427–1435. doi: 10.1172/JCI112120. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gardner P. R., Fridovich I. Superoxide sensitivity of the Escherichia coli 6-phosphogluconate dehydratase. J Biol Chem. 1991 Jan 25;266(3):1478–1483. [PubMed] [Google Scholar]
- Imlay J. A., Linn S. DNA damage and oxygen radical toxicity. Science. 1988 Jun 3;240(4857):1302–1309. doi: 10.1126/science.3287616. [DOI] [PubMed] [Google Scholar]
- Imlay J. A., Linn S. Mutagenesis and stress responses induced in Escherichia coli by hydrogen peroxide. J Bacteriol. 1987 Jul;169(7):2967–2976. doi: 10.1128/jb.169.7.2967-2976.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Johnson K., Charles I., Dougan G., Pickard D., O'Gaora P., Costa G., Ali T., Miller I., Hormaeche C. The role of a stress-response protein in Salmonella typhimurium virulence. Mol Microbiol. 1991 Feb;5(2):401–407. doi: 10.1111/j.1365-2958.1991.tb02122.x. [DOI] [PubMed] [Google Scholar]
- Johnson S. R., Steiner B. M., Cruce D. D., Perkins G. H., Arko R. J. Characterization of a catalase-deficient strain of Neisseria gonorrhoeae: evidence for the significance of catalase in the biology of N. gonorrhoeae. Infect Immun. 1993 Apr;61(4):1232–1238. doi: 10.1128/iai.61.4.1232-1238.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kohashi O., Ono T., Ohki K., Soejima T., Moriya T., Umeda A., Meno Y., Amako K., Funakosi S., Masuda M. Bactericidal activities of rat defensins and synthetic rabbit defensins on Staphylococci, Klebsiella pneumoniae (Chedid, 277, and 8N3), Pseudomonas aeruginosa (mucoid and nonmucoid strains), Salmonella typhimurium (Ra, Rc, Rd, and Re of LPS mutants) and Escherichia coli. Microbiol Immunol. 1992;36(4):369–380. doi: 10.1111/j.1348-0421.1992.tb02036.x. [DOI] [PubMed] [Google Scholar]
- Kono Y., Fridovich I. Superoxide radical inhibits catalase. J Biol Chem. 1982 May 25;257(10):5751–5754. [PubMed] [Google Scholar]
- Lehrer R. I., Barton A., Daher K. A., Harwig S. S., Ganz T., Selsted M. E. Interaction of human defensins with Escherichia coli. Mechanism of bactericidal activity. J Clin Invest. 1989 Aug;84(2):553–561. doi: 10.1172/JCI114198. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mandell G. L. Bactericidal activity of aerobic and anaerobic polymorphonuclear neutrophils. Infect Immun. 1974 Feb;9(2):337–341. doi: 10.1128/iai.9.2.337-341.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McGowan-Jordan I. J., Josephy P. D. Hydroperoxidase I catalyzes peroxidative activation of 3,3'-dichlorobenzidine to a mutagen in Salmonella typhimurium. Arch Biochem Biophys. 1990 Nov 1;282(2):352–357. doi: 10.1016/0003-9861(90)90128-l. [DOI] [PubMed] [Google Scholar]
- Morgan R. W., Christman M. F., Jacobson F. S., Storz G., Ames B. N. Hydrogen peroxide-inducible proteins in Salmonella typhimurium overlap with heat shock and other stress proteins. Proc Natl Acad Sci U S A. 1986 Nov;83(21):8059–8063. doi: 10.1073/pnas.83.21.8059. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mouy R., Fischer A., Vilmer E., Seger R., Griscelli C. Incidence, severity, and prevention of infections in chronic granulomatous disease. J Pediatr. 1989 Apr;114(4 Pt 1):555–560. doi: 10.1016/s0022-3476(89)80693-6. [DOI] [PubMed] [Google Scholar]
- Negri M., Bellavite P., Lauciello C., Guzzo P., Zatti M. A photometric assay for hydrogen peroxide production by polymorphonuclear leucocytes. Clin Chim Acta. 1991 Jul 15;199(3):305–310. doi: 10.1016/0009-8981(91)90124-u. [DOI] [PubMed] [Google Scholar]
- 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]
- Okamura N., Spitznagel J. K. Outer membrane mutants of Salmonella typhimurium LT2 have lipopolysaccharide-dependent resistance to the bactericidal activity of anaerobic human neutrophils. Infect Immun. 1982 Jun;36(3):1086–1095. doi: 10.1128/iai.36.3.1086-1095.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Oliver C. N. Inactivation of enzymes and oxidative modification of proteins by stimulated neutrophils. Arch Biochem Biophys. 1987 Feb 15;253(1):62–72. doi: 10.1016/0003-9861(87)90637-0. [DOI] [PubMed] [Google Scholar]
- Papp-Szabò E., Sutherland C. L., Josephy P. D. Superoxide dismutase and the resistance of Escherichia coli to phagocytic killing by human neutrophils. Infect Immun. 1993 Apr;61(4):1442–1446. doi: 10.1128/iai.61.4.1442-1446.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rajkovic I. A., Williams R. Inhibition of neutrophil function by hydrogen peroxide. Effect of SH-group-containing compounds. Biochem Pharmacol. 1985 Jun 15;34(12):2083–2090. doi: 10.1016/0006-2952(85)90399-5. [DOI] [PubMed] [Google Scholar]
- Royer-Pokora B., Kunkel L. M., Monaco A. P., Goff S. C., Newburger P. E., Baehner R. L., Cole F. S., Curnutte J. T., Orkin S. H. Cloning the gene for an inherited human disorder--chronic granulomatous disease--on the basis of its chromosomal location. Nature. 1986 Jul 3;322(6074):32–38. doi: 10.1038/322032a0. [DOI] [PubMed] [Google Scholar]
- Safe A. F., Maxwell R. T., Howard A. J., Garcia R. C. Relapsing Salmonella enteritidis infection in a young adult male with chronic granulomatous disease. Postgrad Med J. 1991 Feb;67(784):198–201. doi: 10.1136/pgmj.67.784.198. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Saha A. K., Dowling J. N., LaMarco K. L., Das S., Remaley A. T., Olomu N., Pope M. T., Glew R. H. Properties of an acid phosphatase from Legionella micdadei which blocks superoxide anion production by human neutrophils. Arch Biochem Biophys. 1985 Nov 15;243(1):150–160. doi: 10.1016/0003-9861(85)90783-0. [DOI] [PubMed] [Google Scholar]
- Scott M. D., Meshnick S. R., Eaton J. W. Superoxide dismutase-rich bacteria. Paradoxical increase in oxidant toxicity. J Biol Chem. 1987 Mar 15;262(8):3640–3645. [PubMed] [Google Scholar]
- Segal A. W., Abo A. The biochemical basis of the NADPH oxidase of phagocytes. Trends Biochem Sci. 1993 Feb;18(2):43–47. doi: 10.1016/0968-0004(93)90051-n. [DOI] [PubMed] [Google Scholar]
- Selsted M. E., Harwig S. S., Ganz T., Schilling J. W., Lehrer R. I. Primary structures of three human neutrophil defensins. J Clin Invest. 1985 Oct;76(4):1436–1439. doi: 10.1172/JCI112121. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Storz G., Christman M. F., Sies H., Ames B. N. Spontaneous mutagenesis and oxidative damage to DNA in Salmonella typhimurium. Proc Natl Acad Sci U S A. 1987 Dec;84(24):8917–8921. doi: 10.1073/pnas.84.24.8917. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Storz G., Tartaglia L. A., Ames B. N. Transcriptional regulator of oxidative stress-inducible genes: direct activation by oxidation. Science. 1990 Apr 13;248(4952):189–194. doi: 10.1126/science.2183352. [DOI] [PubMed] [Google Scholar]
- Tartaglia L. A., Gimeno C. J., Storz G., Ames B. N. Multidegenerate DNA recognition by the OxyR transcriptional regulator. J Biol Chem. 1992 Jan 25;267(3):2038–2045. [PubMed] [Google Scholar]
- Weitzman S. A., Stossel T. P. Mutation caused by human phagocytes. Science. 1981 May 1;212(4494):546–547. doi: 10.1126/science.6259738. [DOI] [PubMed] [Google Scholar]