{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T22:02:50Z","timestamp":1791842570231,"version":"4.3.4"},"reference-count":90,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2013,12,1]],"date-time":"2013-12-01T00:00:00Z","timestamp":1385856000000},"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":[[2013,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Global proteomic analysis was performed with<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Shigella flexneri<\/jats:named-content>strain 2457T in association with three distinct growth environments:<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. flexneri<\/jats:named-content>growing in broth (<jats:italic>in vitro<\/jats:italic>),<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. flexneri<\/jats:named-content>growing within epithelial cell cytoplasm (intracellular), and<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. flexneri<\/jats:named-content>that were cultured with, but did not invade, Henle cells (extracellular). Compared to<jats:italic>in vitro<\/jats:italic>and extracellular bacteria, intracellular bacteria had increased levels of proteins required for invasion and cell-to-cell spread, including Ipa, Mxi, and Ics proteins. Changes in metabolic pathways in response to the intracellular environment also were evident. There was an increase in glycogen biosynthesis enzymes, altered expression of sugar transporters, and a reduced amount of the carbon storage regulator CsrA. Mixed acid fermentation enzymes were highly expressed intracellularly, while tricarboxylic acid (TCA) cycle oxidoreductive enzymes and most electron transport chain proteins, except CydAB, were markedly decreased. This suggested that fermentation and the CydAB system primarily sustain energy generation intracellularly. Elevated levels of PntAB, which is responsible for NADPH regeneration, suggested a shortage of reducing factors for ATP synthesis. These metabolic changes likely reflect changes in available carbon sources, oxygen levels, and iron availability. Intracellular bacteria showed strong evidence of iron starvation. Iron acquisition systems (Iut, Sit, FhuA, and Feo) and the iron starvation, stress-associated Fe-S cluster assembly (Suf) protein were markedly increased in abundance. Mutational analysis confirmed that the mixed-acid fermentation pathway was required for wild-type intracellular growth and spread of<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. flexneri<\/jats:named-content>. Thus, iron stress and changes in carbon metabolism may be key factors in the<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. flexneri<\/jats:named-content>transition from the extra- to the intracellular milieu.<\/jats:p>","DOI":"10.1128\/iai.00975-13","type":"journal-article","created":{"date-parts":[[2013,10,8]],"date-time":"2013-10-08T00:22:55Z","timestamp":1381191775000},"page":"4635-4648","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":53,"title":["Analysis of the Proteome of Intracellular Shigella flexneri Reveals Pathways Important for Intracellular Growth"],"prefix":"10.1128","volume":"81","author":[{"given":"Rembert","family":"Pieper","sequence":"first","affiliation":[{"name":"J. Craig Venter Institute, Rockville, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. R.","family":"Fisher","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences and Institute for Cellular and Molecular Biology, University of Texas, Austin, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moo-Jin","family":"Suh","sequence":"additional","affiliation":[{"name":"J. Craig Venter Institute, Rockville, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.-T.","family":"Huang","sequence":"additional","affiliation":[{"name":"J. Craig Venter Institute, Rockville, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Parmar","sequence":"additional","affiliation":[{"name":"J. Craig Venter Institute, Rockville, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. M.","family":"Payne","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences and Institute for Cellular and Molecular Biology, University of Texas, Austin, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","first-page":"651","article-title":"Global burden of Shigella infections: implications for vaccine development and implementation of control strategies","volume":"77","author":"Kotloff KL","year":"1999","unstructured":"KotloffKLWinickoffJPIvanoffBClemensJDSwerdlowDLSansonettiPJAdakGKLevineMM. 1999. Global burden of Shigella infections: implications for vaccine development and implementation of control strategies. Bull. World Health Organ. 77:651\u2013666.","journal-title":"Bull. World Health Organ."},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2010.08.014"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.femsre.2003.07.002"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0966-842X(96)10039-1"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1369-5274(99)80009-5"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1814"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2005.00652.x"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6976.2001.tb00569.x"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1001519806727"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.60.1.237-248.1992"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1006\/smim.1999.0175"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.147.3.683"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2001.02200.x"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.3.1254"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1995.tb07243.x"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.51.2.461-469.1986"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.175.8.2189-2196.1993"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.61.12.4941-4946.1993"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.14.6572"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.49.1.164-171.1985"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.170.6.2480-2484.1988"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.4161\/gmic.19325"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.172.11.6274-6281.1990"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00621-07"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1992.tb01385.x"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature08970"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00112-07"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.177.17.5062-5069.1995"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2001.02646.x"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2180-9-110"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2006.05376.x"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1991.tb00762.x"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.175.19.6142-6149.1993"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/embor.2011.132"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0769-2609(86)80040-0"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.32.1.137-144.1981"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.82.6.815-822.1961"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.10.3867"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00589-10"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.66.2.549-557.1998"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.62.11.5168-5172.1994"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.3.1034-1039.2000"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00064-09"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.1.88-102.2005"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00537-13"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.8.4379-4388.2002"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1999.01627.x"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.63.9.3642-3648.1995"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0026554"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.200500253"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2180-10-30"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(06)11009-5"},{"key":"e_1_3_3_54_2","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the false discovery rate: a practical and powerful approach to multiple testing","volume":"57","author":"Benjamini Y","year":"1995","unstructured":"BenjaminiYHochbergY. 1995. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J. R. Stat. Soc. B Methodol. 57:289\u2013300.","journal-title":"J. R. Stat. Soc. B Methodol."},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.200500764"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1186\/1477-5956-7-22"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1021\/ac025747h"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-9-529"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1270"},{"key":"e_1_3_3_60_2","first-page":"13","volume-title":"Escherichia coli and Salmonella: cellular and molecular biology","author":"Neidhardt FC","year":"1996","unstructured":"NeidhardtFCUmbargerHE. 1996. Chemical composition of Escherichia coli, p 13\u201316. In NeidhardtFCCurtissRIIIIngrahamJLRileyMSchaechterMUmbargerHE (ed), Escherichia coli and Salmonella: cellular and molecular biology, 2nd ed. American Society for Microbiology, Washington, DC.","edition":"2"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1038\/msb4100050"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00483-07"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.120163297"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.48.1.124-129.1985"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.11.4179"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2010.06.006"},{"key":"e_1_3_3_67_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1992.tb00885.x"},{"key":"e_1_3_3_68_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2003.03347.x"},{"key":"e_1_3_3_69_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00438-003-0897-0"},{"key":"e_1_3_3_70_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1995.mmi_17010123.x"},{"key":"e_1_3_3_71_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00161-08"},{"key":"e_1_3_3_72_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000140"},{"key":"e_1_3_3_73_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.56.5.1242-1248.1988"},{"key":"e_1_3_3_74_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1998.01021.x"},{"key":"e_1_3_3_75_2","doi-asserted-by":"publisher","DOI":"10.1002\/bit.21219"},{"key":"e_1_3_3_76_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10534-005-4577-x"},{"key":"e_1_3_3_77_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.160.1.266-272.1984"},{"key":"e_1_3_3_78_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0605440103"},{"key":"e_1_3_3_79_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.jbchem.a134996"},{"key":"e_1_3_3_80_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.61.9.3625-3635.1993"},{"key":"e_1_3_3_81_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.resmic.2013.06.008"},{"key":"e_1_3_3_82_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1672-0229(07)60021-7"},{"key":"e_1_3_3_83_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1999.01397.x"},{"key":"e_1_3_3_84_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2013.04.031"},{"key":"e_1_3_3_85_2","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.200900196"},{"key":"e_1_3_3_86_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2180-11-147"},{"key":"e_1_3_3_87_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.65.2.818-821.1997"},{"key":"e_1_3_3_88_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.032066599"},{"key":"e_1_3_3_89_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01211-07"},{"key":"e_1_3_3_90_2","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M900446-MCP200"},{"key":"e_1_3_3_91_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.155.3.949-955.1983"}],"container-title":["Infection and Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.00975-13","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.00975-13","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,18]],"date-time":"2024-05-18T13:29:52Z","timestamp":1716038992000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/IAI.00975-13"}},"subtitle":[],"editor":[{"given":"F. C.","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2013,12]]},"references-count":90,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2013,12]]}},"alternative-id":["10.1128\/IAI.00975-13"],"URL":"https:\/\/doi.org\/10.1128\/iai.00975-13","relation":{},"ISSN":["0019-9567","1098-5522"],"issn-type":[{"value":"0019-9567","type":"print"},{"value":"1098-5522","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,12]]},"assertion":[{"value":"2013-08-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-09-30","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-11-13","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}