{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T10:30:54Z","timestamp":1749033054531},"reference-count":52,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2013,9,1]],"date-time":"2013-09-01T00:00:00Z","timestamp":1377993600000},"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":[[2013,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Shigella<\/jats:named-content>\n            species Gram-negative bacteria which cause a diarrheal disease, known as shigellosis, by invading and destroying the colonic mucosa and inducing a robust inflammatory response. With no vaccine available, shigellosis annually kills over 600,000 children in developing countries. This study demonstrates the utility of combining high-throughput bioinformatic methods with\n            <jats:italic>in vitro<\/jats:italic>\n            and\n            <jats:italic>in vivo<\/jats:italic>\n            assays to provide new insights into pathogenesis. Comparisons of\n            <jats:italic>in vivo<\/jats:italic>\n            and\n            <jats:italic>in vitro<\/jats:italic>\n            gene expression identified genes associated with intracellular growth. Additional bioinformatics analyses identified genes that are present in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. flexneri<\/jats:named-content>\n            isolates but not in the three other\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Shigella<\/jats:named-content>\n            species. Comparison of these two analyses revealed nine genes that are differentially expressed during invasion and that are specific to\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. flexneri<\/jats:named-content>\n            . One gene, a DeoR family transcriptional regulator with decreased expression during invasion, was further characterized and is now designated\n            <jats:italic>icgR<\/jats:italic>\n            , for\n            <jats:underline>i<\/jats:underline>\n            ntra\n            <jats:underline>c<\/jats:underline>\n            ellular\n            <jats:underline>g<\/jats:underline>\n            rowth\n            <jats:underline>r<\/jats:underline>\n            egulator. Deletion of\n            <jats:italic>icgR<\/jats:italic>\n            caused no difference in growth\n            <jats:italic>in vitro<\/jats:italic>\n            but resulted in increased intracellular replication in HCT-8 cells. Further\n            <jats:italic>in vitro<\/jats:italic>\n            and\n            <jats:italic>in vivo<\/jats:italic>\n            studies using high-throughput sequencing of RNA transcripts (RNA-seq) of an isogenic \u0394\n            <jats:italic>icgR<\/jats:italic>\n            mutant identified 34 genes that were upregulated under both growth conditions. This combined informatics and functional approach has allowed the characterization of a gene and pathway previously unknown in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Shigella<\/jats:named-content>\n            pathogenesis and provides a framework for further identification of novel virulence factors and regulatory pathways.\n          <\/jats:p>","DOI":"10.1128\/iai.00537-13","type":"journal-article","created":{"date-parts":[[2013,6,11]],"date-time":"2013-06-11T03:17:08Z","timestamp":1370920628000},"page":"3068-3076","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":14,"title":["Characterization of Intracellular Growth Regulator\n            <i>icgR<\/i>\n            by Utilizing Transcriptomics To Identify Mediators of Pathogenesis in Shigella flexneri"],"prefix":"10.1128","volume":"81","author":[{"given":"Carolyn R.","family":"Morris","sequence":"first","affiliation":[{"name":"Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, USA"},{"name":"Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA"},{"name":"Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christen L.","family":"Grassel","sequence":"additional","affiliation":[{"name":"Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia C.","family":"Redman","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA"},{"name":"Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason W.","family":"Sahl","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA"},{"name":"Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eileen M.","family":"Barry","sequence":"additional","affiliation":[{"name":"Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, USA"},{"name":"Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David A.","family":"Rasko","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA"},{"name":"Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2000.0599"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.35.3.852-860.1982"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.59.6.1997-2005.1991"},{"key":"e_1_3_3_5_2","first-page":"454","article-title":"Shigellosis: challenges and management issues","volume":"120","author":"Sur D","year":"2004","unstructured":"SurDRamamurthyTDeenJBhattacharyaSK. 2004. 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