{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T11:43:03Z","timestamp":1791114183076,"version":"4.1.0"},"reference-count":41,"publisher":"American Society for Cell Biology (ASCB)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MBoC"],"published-print":{"date-parts":[[2006,1]]},"abstract":"<jats:p>\n                    The objective of these studies was to analyze the role of the ionic environment of phagosomal vacuoles in the control of pathogens by macrophages. Digital imaging and flow cytometry were used to follow the induction of the phoP promoter of Salmonella enterica Typhimurium within live macrophages. Manipulating the Mg\n                    <jats:sup>2+<\/jats:sup>\n                    concentration within the Salmonella-containing vacuole (SCV) was without effect on the early induction of PhoPQ. Moreover, direct measurement of [Mg\n                    <jats:sup>2+<\/jats:sup>\n                    ] within the SCV using nanosensor particles showed that, during this initial period of phoP activation, the concentration of the divalent cation is rapidly regulated and stabilizes around 1 mm. Extrusion of other divalent cations via the Nramp1 efflux pump was similarly ruled out as an important contributor to the activation of the regulon. By contrast, induction of PhoP was greatly attenuated when the pH gradient across the SCV membrane was dissipated. A second, more modest pH-independent component of PhoP induction was unmasked by inhibition of the vacuolar proton pump. This second component was eliminated by pretreatment of cells with IFN\u03b3, even though the cytokine augmented the overall PhoP response. These findings demonstrate the existence of at least three separate activators of phoP transcription: resting and IFN\u03b3-stimulated pH-sensitive components, plus a pH-independent component.\n                  <\/jats:p>","DOI":"10.1091\/mbc.e04-12-1096","type":"journal-article","created":{"date-parts":[[2005,10,26]],"date-time":"2005-10-26T20:43:27Z","timestamp":1130359407000},"page":"498-510","source":"Crossref","is-referenced-by-count":112,"title":["Visualization of Vacuolar Acidification-induced Transcription of Genes of Pathogens inside Macrophages"],"prefix":"10.1091","volume":"17","author":[{"given":"Natalia","family":"Martin-Orozco","sequence":"first","affiliation":[{"name":"Cell Biology Program, Hospital for Sick Children and Department of Biochemistry, University of Toronto, Toronto, Ontario M5G 1X8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Touret","sequence":"additional","affiliation":[{"name":"Cell Biology Program, Hospital for Sick Children and Department of Biochemistry, University of Toronto, Toronto, Ontario M5G 1X8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael L.","family":"Zaharik","sequence":"additional","affiliation":[{"name":"Biotechnology Laboratory, University of British Columbia, Vancouver, British Columbia V6T1Z3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edwin","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Michigan, Ann Arbor, MI 48109-1055"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raoul","family":"Kopelman","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Michigan, Ann Arbor, MI 48109-1055"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Laboratory of Medicine, University of Washington Medical School, Seattle, WA 98195"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. Brett","family":"Finlay","sequence":"additional","affiliation":[{"name":"Biotechnology Laboratory, University of British Columbia, Vancouver, British Columbia V6T1Z3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Gros","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Center for the Study of Host Resistance, McGill University, Montreal, Quebec, Canada H3A 2T5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Grinstein","sequence":"additional","affiliation":[{"name":"Cell Biology Program, Hospital for Sick Children and Department of Biochemistry, University of Toronto, Toronto, Ontario M5G 1X8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1076","reference":[{"key":"REF1","doi-asserted-by":"crossref","unstructured":"Alpuche Aranda, C. M., Swanson, J. A., Loomis, W. P., and Miller, S. I. 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Dis.\n                      14\n                      , 573-578.","DOI":"10.1097\/00001432-200110000-00011"},{"key":"REF22","unstructured":"Jabado, N., Tseung-Yuk-Lam, S., Forbes, J. R., and Gros, P. (2004). Mouse natural resistance associated macrophage protein 1 (Nramp1): a key regulator of host innate immunity against infections. In:\n                      The Nramp Family\n                      , ed. Cellier, M., and Gros, P., New York: Kluwer Academic\/Plenum Publishers, 1-15."},{"key":"REF23","doi-asserted-by":"crossref","unstructured":"Lejona, S., Castelli, M. E., Cabeza, M. L., Kenney, L. J., Garcia Vescovi, E., and Soncini, F. C. (2004). PhoP can activate its target genes in a PhoQ-independent manner.\n                      J Bacteriol.\n                      186\n                      , 2476-2480.","DOI":"10.1128\/JB.186.8.2476-2480.2004"},{"key":"REF24","doi-asserted-by":"crossref","unstructured":"Mastroeni, P., Harrison, J. A., Robinson, J. H., Clare, S., Khan, S., Maskell, D. J., Dougan, G., and Hormaeche, C. E. (1998). Interleukin-12 is required for control of the growth of attenuated aromatic-compound-dependent salmonellae in BALB\/c mice: role of gamma interferon and macrophage activation.\n                      Infect. Immun.\n                      66\n                      , 4767-4776.","DOI":"10.1128\/IAI.66.10.4767-4776.1998"},{"key":"REF25","doi-asserted-by":"crossref","unstructured":"Miller, S. I., Kukral, A. M., and Mekalanos, J. J. (1989). A two-component regulatory system (phoP phoQ) controls\n                      Salmonella typhimurium\n                      virulence.\n                      Proc. Natl. Acad. Sci. USA\n                      86\n                      , 5054-5058.","DOI":"10.1073\/pnas.86.13.5054"},{"key":"REF26","doi-asserted-by":"crossref","unstructured":"Mirza, S. H., Beeching, N. J., and Hart, C. A. (1996). Multi-drug resistant typhoid: a global problem.\n                      J. Med. Microbiol.\n                      44\n                      , 317-319.","DOI":"10.1099\/00222615-44-5-317"},{"key":"REF27","doi-asserted-by":"crossref","unstructured":"Monack, D. M., Bouley, D. M., and Falkow, S. (2004).\n                      Salmonella typhimurium\n                      persists within macrophages in the mesenteric lymph nodes of chronically infected Nramp1+\/+ mice and can be reactivated by IFN\u03b3 neutralization.\n                      J. Exp. Med.\n                      199\n                      , 231-241.","DOI":"10.1084\/jem.20031319"},{"key":"REF28","doi-asserted-by":"crossref","unstructured":"Nauciel, C., and Espinasse-Maes, F. (1992). Role of gamma interferon and tumor necrosis factor alpha in resistance to\n                      Salmonella typhimurium\n                      infection.\n                      Infect. Immun.\n                      60\n                      , 450-454.","DOI":"10.1128\/IAI.60.2.450-454.1992"},{"key":"REF29","doi-asserted-by":"crossref","unstructured":"Park, E. J., Brasuel, M., Behrend, C., Philbert, M. A., and Kopelman, R. (2003). Ratiometric optical PEBBLE nanosensors for real-time magnesium ion concentrations inside viable cells.\n                      Anal. Chem.\n                      75\n                      , 3784-3791.","DOI":"10.1021\/ac0342323"},{"key":"REF30","doi-asserted-by":"crossref","unstructured":"Pie, S., Truffa-Bachi, P., Pla, M., and Nauciel, C. (1997). Th1 response in\n                      Salmonella typhimurium\n                      -infected mice with a high or low rate of bacterial clearance.\n                      Infect. Immun.\n                      65\n                      , 4509-4514.","DOI":"10.1128\/IAI.65.11.4509-4514.1997"},{"key":"REF31","doi-asserted-by":"crossref","unstructured":"Rathman, M., Sjaastad, M. D., and Falkow, S. (1996). Acidification of phagosomes containing\n                      Salmonella typhimurium\n                      in murine macrophages.\n                      Infect. Immun.\n                      64\n                      , 2765-2773.","DOI":"10.1128\/IAI.64.7.2765-2773.1996"},{"key":"REF32","doi-asserted-by":"crossref","unstructured":"Rosenberger, C. M., Gallo, R. L., and Finlay, B. B. (2004). Interplay between antibacterial effectors: a macrophage antimicrobial peptide impairs intracellular\n                      Salmonella\n                      replication.\n                      Proc. Natl. Acad. Sci. USA\n                      101\n                      , 2422-2427.","DOI":"10.1073\/pnas.0304455101"},{"key":"REF33","doi-asserted-by":"crossref","unstructured":"Shea, J. E., Hensel, M., Gleeson, C., and Holden, D. W. (1996). Identification of a virulence locus encoding a second type III secretion system in\n                      Salmonella typhimurium\n                      .\n                      Proc. Natl. Acad. Sci. USA\n                      93\n                      , 2593-2597.","DOI":"10.1073\/pnas.93.6.2593"},{"key":"REF34","doi-asserted-by":"crossref","unstructured":"Soncini, F. C., Garcia Vescovi, E., Solomon, F., and Groisman, E. A. (1996). Molecular basis of the magnesium deprivation response in\n                      Salmonella typhimurium\n                      : identification of PhoP-regulated genes.\n                      J. Bacteriol.\n                      178\n                      , 5092-5099.","DOI":"10.1128\/jb.178.17.5092-5099.1996"},{"key":"REF35","doi-asserted-by":"crossref","unstructured":"Soncini, F. C., Vescovi, E. G., and Groisman, E. A. (1995). 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Effects on microbial killing by activated peritoneal macrophages in vitro.\n                      J. Exp. Med.\n                      192\n                      , 227-236.","DOI":"10.1084\/jem.192.2.227"},{"key":"REF38","doi-asserted-by":"crossref","unstructured":"Wick, M. J. (2004). Living in the danger zone: innate immunity to\n                      Salmonella\n                      .\n                      Curr. Opin. Microbiol.\n                      7\n                      , 51-57.","DOI":"10.1016\/j.mib.2003.12.008"},{"key":"REF39","doi-asserted-by":"crossref","unstructured":"Yoshimori, T., Yamamoto, A., Moriyama, Y., Futai, M., and Tashiro, Y. (1991). Bafilomycin A1, a specific inhibitor of vacuolar-type H(+)-ATPase, inhibits acidification and protein degradation in lysosomes of cultured cells.\n                      J. Biol. Chem.\n                      266\n                      , 17707-17712.","DOI":"10.1016\/S0021-9258(19)47429-2"},{"key":"REF40","doi-asserted-by":"crossref","unstructured":"Young, D., Hussell, T., and Dougan, G. (2002). Chronic bacterial infections: living with unwanted guests.\n                      Nat. Immunol.\n                      3\n                      , 1026-1032.","DOI":"10.1038\/ni1102-1026"},{"key":"REF41","doi-asserted-by":"crossref","unstructured":"Zaharik, M. L., Cullen, V. L., Fung, A. M., Libby, S. J., Kujat Choy, S. L., Coburn, B., Kehres, D. G., Maguire, M. E., Fang, F. C., and Finlay, B. B. (2004). The\n                      Salmonella enterica\n                      serovar typhimurium divalent cation transport systems MntH and SitABCD are essential for virulence in an Nramp1G169 murine typhoid model.\n                      Infect. Immun.\n                      72\n                      , 5522-5525.","DOI":"10.1128\/IAI.72.9.5522-5525.2004"}],"container-title":["Molecular Biology of the Cell"],"original-title":[],"language":"en","deposited":{"date-parts":[[2021,7,18]],"date-time":"2021-07-18T18:14:37Z","timestamp":1626632077000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.molbiolcell.org\/doi\/10.1091\/mbc.e04-12-1096"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,1]]},"references-count":41,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2006,1]]}},"alternative-id":["10.1091\/mbc.e04-12-1096"],"URL":"https:\/\/doi.org\/10.1091\/mbc.e04-12-1096","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1029765.346573","asserted-by":"object"}]},"ISSN":["1059-1524","1939-4586"],"issn-type":[{"value":"1059-1524","type":"print"},{"value":"1939-4586","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,1]]}}}