{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T11:48:37Z","timestamp":1789818517696,"version":"4.0.1"},"reference-count":49,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2003,6,1]],"date-time":"2003-06-01T00:00:00Z","timestamp":1054425600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2003,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Two acidified nitrite-inducible genes of<jats:italic>Salmonella enterica<\/jats:italic>serovar Typhimurium were identified with a green fluorescent protein-based promoter-trap screen. The nitrite-inducible promoters were located upstream of loci that we designated<jats:italic>nipAB<\/jats:italic>and<jats:italic>nipC<\/jats:italic>, which correspond to<jats:italic>hcp-hcr<\/jats:italic>(hybrid cluster protein) of<jats:italic>Escherichia coli<\/jats:italic>and<jats:italic>norA<\/jats:italic>of<jats:italic>Alcaligenes eutrophus<\/jats:italic>, respectively. Maximal induction of the promoters by nitrite was dependent on pH. The<jats:italic>nipAB<\/jats:italic>promoter was regulated by oxygen in an Fnr-dependent manner. The<jats:italic>nipC<\/jats:italic>promoter was also regulated by oxygen but in an Fnr-independent manner. The promoters were upregulated in activated RAW264.7 macrophage-like cells, which produce NO via the inducible nitric oxide synthase (iNOS), and the induction was inhibited by aminoguanidine, an inhibitor of iNOS. Although the<jats:italic>nipAB<\/jats:italic>and<jats:italic>nipC<\/jats:italic>mutants displayed no defects under a variety of in vitro conditions or in tissue culture infections, they exhibited lower oral 50% lethal doses (LD<jats:sub>50<\/jats:sub>s) than did the wild type in C57BL\/6J mouse infections. The lower LD<jats:sub>50<\/jats:sub>s reflected an unexpected increased ability of small inoculating doses of the mutant bacteria to cause lethal infection 2 to 3 weeks after challenge, compared to a similar challenge dose of wild-type bacteria. We conclude that these genes are regulated by physiological nitrogen oxides and that the absence of these bacterial genes in some way diminishes the ability of mice to clear a low dose infection.<\/jats:p>","DOI":"10.1128\/iai.71.6.3196-3205.2003","type":"journal-article","created":{"date-parts":[[2003,5,21]],"date-time":"2003-05-21T23:33:12Z","timestamp":1053559992000},"page":"3196-3205","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":52,"title":["Modulation of Virulence by Two Acidified Nitrite-Responsive Loci of<i>Salmonella enterica<\/i>Serovar Typhimurium"],"prefix":"10.1128","volume":"71","author":[{"given":"Charles C.","family":"Kim","sequence":"first","affiliation":[{"name":"Microbiology and Immunology, Stanford University Medical Center, Stanford, California 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise","family":"Monack","sequence":"additional","affiliation":[{"name":"Microbiology and Immunology, Stanford University Medical Center, Stanford, California 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanley","family":"Falkow","sequence":"additional","affiliation":[{"name":"Microbiology and Immunology, Stanford University Medical Center, Stanford, California 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s007750050210"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1021\/ac9810462"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(96)69027-2"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1998.01048.x"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi001483m"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.179.21.6769-6777.1997"},{"key":"e_1_3_2_8_2","unstructured":"Daniels L. R. S. Hanson and J. A. Phillips. 1994. Chemical analysis p. 512-554. In P. Gerhardt R. G. E. Murray W. A. Wood and N. R. Krieg (ed.) Methods for general and molecular bacteriology. ASM Press Washington D.C."},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.120163297"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1286-4579(01)01482-4"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1119(02)00551-6"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1462-5822.2000.00051.x"},{"key":"e_1_3_2_13_2","doi-asserted-by":"crossref","first-page":"1820","DOI":"10.4049\/jimmunol.159.4.1820","volume":"159","year":"1997","unstructured":"Everest, P., J. Allen, A. Papakonstantinopoulou, P. Mastroeni, M. Roberts, and G. Dougan. 1997. Salmonella typhimurium infections in mice deficient in interleukin-4 production: role of IL-4 in infection-associated pathology. J. Immunol.159:1820-1827.","journal-title":"J. Immunol."},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119473"},{"key":"e_1_3_2_15_2","unstructured":"Feelisch M. and J. S. Stamler. 1996. Donors of nitrogen oxides p. 71-115. In M. Feelisch and J. S. Stamler (ed.) Methods in nitric oxide research. John Wiley & Sons New York N.Y."},{"key":"e_1_3_2_16_2","unstructured":"Gennis R. B. and V. Stewart. 1996. Respiration p. 217-261. In F. C. Neidhardt R. Curtiss III J. L. Ingraham E. C. C. Lin K. B. Low B. Magasanik W. S. Reznikoff M. Riley M. Schaechter and H. E. Umbarger (ed.) Escherichia coli and Salmonella : cellular and molecular biology 2nd ed. vol. 1. ASM Press Washington D.C."},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.183.2.611-620.2001"},{"key":"e_1_3_2_18_2","first-page":"319","volume":"37","year":"1979","unstructured":"Hormaeche, C. E. 1979. Genetics of natural resistance to salmonellae in mice. Immunology37:319-327.","journal-title":"Immunology"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-1759(94)90021-3"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1996.0557"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.2.451-461.2002"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.178.21.6238-6249.1996"},{"key":"e_1_3_2_23_2","unstructured":"Lynch A. S. and E. C. C. Lin. 1996. Responses to molecular oxygen p. 1526-1538. In F. C. Neidhardt R. Curtiss III J. L. Ingraham E. C. C. Lin K. B. Low B. Magasanik W. S. Reznikoff M. Riley M. Schaechter and H. E. Umbarger (ed.) Escherichia coli and Salmonella : cellular and molecular biology 2nd ed. vol. 2. ASM Press Washington D.C."},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.15.1.323"},{"key":"e_1_3_2_25_2","first-page":"G745","volume":"277","year":"1999","unstructured":"Mashimo, H., and R. K. Goyal. 1999. Lessons from genetically engineered animal models. IV. Nitric oxide synthase gene knockout mice. Am. J. Physiol.277:G745-G750.","journal-title":"Am. J. Physiol."},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.192.2.237"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/35101614"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00267425"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1099\/00222615-14-4-419"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.60.7.2758-2768.1992"},{"key":"e_1_3_2_31_2","doi-asserted-by":"crossref","first-page":"3313","DOI":"10.4049\/jimmunol.133.6.3313","volume":"133","year":"1984","unstructured":"O'Brien, A. D., B. A. Taylor, and D. L. Rosenstreich. 1984. Genetic control of natural resistance to Salmonella typhimurium in mice during the late phase of infection. J. Immunol.133:3313-3318.","journal-title":"J. Immunol."},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2000.02157.x"},{"key":"e_1_3_2_33_2","first-page":"493","volume":"27","year":"1938","unstructured":"Reed, L. J., and H. Muench. 1938. A simple method of Estimating fifty per cent endpoints. Am. J. Hyg.27:493-497.","journal-title":"Am. J. Hyg."},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.186.4.569"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80004-7"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1369-5274(99)00048-X"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1119(87)90095-3"},{"key":"e_1_3_2_38_2","first-page":"59","volume":"45","year":"1984","unstructured":"Smith, B. P., M. Reinaguerra, S. K. Hoiseth, B. A. D. Stocker, F. Habasha, E. Johnson, and F. Merritt. 1984. Aromatic-dependent Salmonella-typhimurium as modified live vaccines for calves. Am. J. Vet. Res.45:59-66.","journal-title":"Am. J. Vet. Res."},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(95)02099-3"},{"key":"e_1_3_2_40_2","first-page":"399","volume":"6","year":"1990","unstructured":"Spiro, S., and J. R. Guest. 1990. FNR and its role in oxygen-regulated gene expression in Escherichia coli. FEMS Microbiol. Rev.6:399-428.","journal-title":"FEMS Microbiol. Rev."},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.67.1.509"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1993.tb01106.x"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1996.00120.x"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5334.2007"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1327.2000.01032.x"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.192.2.227"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.183.8.2516-2526.2001"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.69.10.6391-6400.2001"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.184.21.5898-5902.2002"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.2468181"}],"container-title":["Infection and Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.71.6.3196-3205.2003","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.71.6.3196-3205.2003","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,26]],"date-time":"2023-04-26T09:10:04Z","timestamp":1682500204000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/IAI.71.6.3196-3205.2003"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,6]]},"references-count":49,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2003,6]]}},"alternative-id":["10.1128\/IAI.71.6.3196-3205.2003"],"URL":"https:\/\/doi.org\/10.1128\/iai.71.6.3196-3205.2003","relation":{},"ISSN":["0019-9567","1098-5522"],"issn-type":[{"value":"0019-9567","type":"print"},{"value":"1098-5522","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,6]]},"assertion":[{"value":"2002-10-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2003-03-18","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2003-06-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}