{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T08:05:52Z","timestamp":1792569952568,"version":"4.5.0"},"reference-count":40,"publisher":"National Academy of Sciences","issue":"24","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2002,11,26]]},"abstract":"<jats:p>\n                    <jats:italic>Nramp1<\/jats:italic>\n                    (\n                    <jats:italic>N<\/jats:italic>\n                    atural\n                    <jats:italic>r<\/jats:italic>\n                    esistance-\n                    <jats:italic>a<\/jats:italic>\n                    ssociated\n                    <jats:italic>m<\/jats:italic>\n                    acrophage\n                    <jats:italic>p<\/jats:italic>\n                    rotein-\n                    <jats:italic>1<\/jats:italic>\n                    ; also known as Slc11a1) is a host resistance gene that provides protection against several intracellular pathogens, including\n                    <jats:italic>Salmonella<\/jats:italic>\n                    <jats:italic>enterica<\/jats:italic>\n                    serovar Typhimurium. Little is known about the dynamic interplay that occurs between mammalian host resistance determinants such as Nramp1 and pathogens during infection. To explore these interactions, we examined the effect of Nramp1 on expression of\n                    <jats:italic>Salmonella typhimurium<\/jats:italic>\n                    (STM) virulence factors. We demonstrate that\n                    <jats:italic>Salmonella<\/jats:italic>\n                    pathogenicity island\n                    <jats:italic>2<\/jats:italic>\n                    (SPI2) is essential for replication of STM in spleens of infected\n                    <jats:italic>Nramp1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>+\/+<\/jats:italic>\n                    <\/jats:sup>\n                    mice. Furthermore, the presence of Nramp1 in transfected cell lines and congenic knockout mice resulted in the up-regulation of STM SPI2-associated virulence genes critical for intramacrophage survival. This Nramp1-dependent up-regulation of SPI2 was mimicked\n                    <jats:italic>in vitro<\/jats:italic>\n                    by chelation of iron, demonstrating the iron-responsive nature of expression of STM SPI2-associated virulence genes. We propose that acquisition of SPI2 by\n                    <jats:italic>S. enterica<\/jats:italic>\n                    not only enabled this bacterium to become an effective intracellular pathogen but also allowed the bacterium to withstand the effects of macrophage defense mechanisms such as Nramp1 early in the evolution of its pathogenic character. These dynamic Nramp1\u2013pathogen interactions may be essential for regulating the course of an infection. This study demonstrates the presence of a previously undescribed direct influence of a mammalian innate host resistance locus on a pathogen at the genetic level.\n                  <\/jats:p>","DOI":"10.1073\/pnas.252415599","type":"journal-article","created":{"date-parts":[[2002,11,26]],"date-time":"2002-11-26T12:42:52Z","timestamp":1038314572000},"page":"15705-15710","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":82,"title":["Host\u2013pathogen interactions: Host resistance factor Nramp1 up-regulates the expression of\n                    <i>Salmonella<\/i>\n                    pathogenicity island-2 virulence genes"],"prefix":"10.1073","volume":"99","author":[{"given":"Michelle L.","family":"Zaharik","sequence":"first","affiliation":[{"name":"Biotechnology Laboratory and Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC, Canada V6T 1Z3 North America; Department of Molecular Microbiology, Instituto de Biotecnolog\u00eda, Universidad Nacional Aut\u00f3noma de Mexico North America, Cuernavaca, Morelos, 62250 M\u00e9xico; and Department of Biochemistry and Center for the Study of Host Resistance, McGill University, Montreal, QE, Canada H3G 1Y6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce A.","family":"Vallance","sequence":"additional","affiliation":[{"name":"Biotechnology Laboratory and Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC, Canada V6T 1Z3 North America; Department of Molecular Microbiology, Instituto de Biotecnolog\u00eda, Universidad Nacional Aut\u00f3noma de Mexico North America, Cuernavaca, Morelos, 62250 M\u00e9xico; and Department of Biochemistry and Center for the Study of Host Resistance, McGill University, Montreal, QE, Canada H3G 1Y6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 L.","family":"Puente","sequence":"additional","affiliation":[{"name":"Biotechnology Laboratory and Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC, Canada V6T 1Z3 North America; Department of Molecular Microbiology, Instituto de Biotecnolog\u00eda, Universidad Nacional Aut\u00f3noma de Mexico North America, Cuernavaca, Morelos, 62250 M\u00e9xico; and Department of Biochemistry and Center for the Study of Host Resistance, McGill University, Montreal, QE, Canada H3G 1Y6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Gros","sequence":"additional","affiliation":[{"name":"Biotechnology Laboratory and Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC, Canada V6T 1Z3 North America; Department of Molecular Microbiology, Instituto de Biotecnolog\u00eda, Universidad Nacional Aut\u00f3noma de Mexico North America, Cuernavaca, Morelos, 62250 M\u00e9xico; and Department of Biochemistry and Center for the Study of Host Resistance, McGill University, Montreal, QE, Canada H3G 1Y6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. Brett","family":"Finlay","sequence":"additional","affiliation":[{"name":"Biotechnology Laboratory and Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC, Canada V6T 1Z3 North America; Department of Molecular Microbiology, Instituto de Biotecnolog\u00eda, Universidad Nacional Aut\u00f3noma de Mexico North America, Cuernavaca, Morelos, 62250 M\u00e9xico; and Department of Biochemistry and Center for the Study of Host Resistance, McGill University, Montreal, QE, Canada H3G 1Y6"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2002,11,19]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.191288998"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1369-5274(99)00049-1"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s000110050330"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1462-5822.2001.00150.x"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3540511"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2567.1999.00672.x"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3630089"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1286-4579(00)00273-2"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1286-4579(01)01490-3"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.6.2593"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1998.01047.x"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.5.2225-2232.1999"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M105508200"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1119(87)90051-5"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1999.01312.x"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2000.01922.x"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.182.3.655"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2002.02820.x"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1998.01048.x"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.15.7800"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.1.213-219.1999"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.64.8.2923-2929.1996"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.192.9.1237"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.182.3.771-781.2000"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2002.02912.x"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.182.7.1872-1882.2000"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5334.2007"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.11.5690-5698.1999"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2001.02593.x"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2002.02821.x"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2000.01783.x"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.174.13.4317-4323.1992"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)00092-1"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.183.6.1835-1842.2001"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.188.2.351"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1462-5822.2002.00213.x"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.287.5458.1655"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20011547"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.192.2.227"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.192.2.237"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.252415599","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T09:30:57Z","timestamp":1649842257000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.252415599"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,11,19]]},"references-count":40,"journal-issue":{"issue":"24","published-print":{"date-parts":[[2002,11,26]]}},"alternative-id":["10.1073\/pnas.252415599"],"URL":"https:\/\/doi.org\/10.1073\/pnas.252415599","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,11,19]]},"assertion":[{"value":"2002-07-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2002-11-19","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}