{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T16:18:38Z","timestamp":1781108318253,"version":"3.54.1"},"reference-count":46,"publisher":"National Academy of Sciences","issue":"10","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2009,3,10]]},"abstract":"<jats:p>\n                    The acquisition of DNA by horizontal gene transfer enables bacteria to adapt to previously unexploited ecological niches. Although horizontal gene transfer and mutation of protein-coding sequences are well-recognized forms of pathogen evolution, the evolutionary significance of\n                    <jats:italic>cis<\/jats:italic>\n                    -regulatory mutations in creating phenotypic diversity through altered transcriptional outputs is not known. We show the significance of regulatory mutation for pathogen evolution by mapping and then rewiring a\n                    <jats:italic>cis<\/jats:italic>\n                    -regulatory module controlling a gene required for murine typhoid. Acquisition of a binding site for the\n                    <jats:italic>Salmonella<\/jats:italic>\n                    pathogenicity island-2 regulator, SsrB, enabled the\n                    <jats:italic>srfN<\/jats:italic>\n                    gene, ancestral to the\n                    <jats:italic>Salmonella<\/jats:italic>\n                    genus, to play a role in pathoadaptation of\n                    <jats:italic>S. typhimurium<\/jats:italic>\n                    to a host animal. We identified the evolved\n                    <jats:italic>cis<\/jats:italic>\n                    -regulatory module and quantified the fitness gain that this regulatory output accrues for the bacterium using competitive infections of host animals. Our findings highlight a mechanism of pathogen evolution involving regulatory mutation that is selected because of the fitness advantage the new regulatory output provides the incipient clones.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0811669106","type":"journal-article","created":{"date-parts":[[2009,2,21]],"date-time":"2009-02-21T22:33:01Z","timestamp":1235255581000},"page":"3982-3987","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":54,"title":["Pathogenic adaptation of intracellular bacteria by rewiring a\n                    <i>cis<\/i>\n                    -regulatory input function"],"prefix":"10.1073","volume":"106","author":[{"given":"Suzanne E.","family":"Osborne","sequence":"first","affiliation":[{"name":"The Michael G. DeGroote Institute for Infectious Disease Research, Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada L8N 3Z5;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Don","family":"Walthers","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Illinois, Chicago, IL 60612;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana M.","family":"Tomljenovic","sequence":"additional","affiliation":[{"name":"The Michael G. DeGroote Institute for Infectious Disease Research, Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada L8N 3Z5;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David T.","family":"Mulder","sequence":"additional","affiliation":[{"name":"The Michael G. DeGroote Institute for Infectious Disease Research, Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada L8N 3Z5;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uma","family":"Silphaduang","sequence":"additional","affiliation":[{"name":"The Michael G. DeGroote Institute for Infectious Disease Research, Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada L8N 3Z5;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Duong","sequence":"additional","affiliation":[{"name":"The Michael G. DeGroote Institute for Infectious Disease Research, Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada L8N 3Z5;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Lowden","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Dartmouth College, Hanover, NH 03755;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark E.","family":"Wickham","sequence":"additional","affiliation":[{"name":"Phillips Ormonde &amp; Fitzpatrick, 367 Collins Street, Melbourne, Victoria, 3000, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ross F.","family":"Waller","sequence":"additional","affiliation":[{"name":"School of Botany, University of Melbourne, Melbourne, Victoria, 3010, Australia; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda J.","family":"Kenney","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Illinois, Chicago, IL 60612;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian K.","family":"Coombes","sequence":"additional","affiliation":[{"name":"The Michael G. DeGroote Institute for Infectious Disease Research, Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada L8N 3Z5;"},{"name":"Public Health Agency of Canada, Laboratory for Foodborne Zoonoses, Guelph, ON, Canada N1G 3W4"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2009,3,10]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro884"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.15.7800"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.6.2593"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2004.04317.x"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2007.05800.x"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg700"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1478"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2005.04668.x"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.182.3.771-781.2000"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2003.03502.x"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2005.04553.x"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.252415599"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0040045"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01763"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0030245"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80868-5"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0505401102"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/elps.1150190413"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/nsb845"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0966-842X(97)01082-2"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.16.7252"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg1615"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msh105"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0406038101"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.0020011"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/35012500"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2005.09.007"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.0020209"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.7.3943"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.01.014"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature06151"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2063"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1558-5646.2007.00105.x"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0700488104"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng2104"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1620408"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1105\/tpc.106.048694"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0605565104"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.0020042"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04597"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M707352200"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.5.2879-2888.2004"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M404299200"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.molbev.a025664"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.molbev.a026231"},{"key":"e_1_3_3_46_2","article-title":"Structural and functional analysis of the C-terminal DNA binding domain of the Salmonella Typhimurium SPI-2 response regulator SsrB","author":"Liao X","year":"2009","unstructured":"X Liao, et al., Structural and functional analysis of the C-terminal DNA binding domain of the Salmonella Typhimurium SPI-2 response regulator SsrB. 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