{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T21:20:29Z","timestamp":1792704029300,"version":"4.5.0"},"reference-count":54,"publisher":"National Academy of Sciences","issue":"25","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1996,12,10]]},"abstract":"<jats:p>\n                    <jats:italic>cagA<\/jats:italic>\n                    , a gene that codes for an immunodominant\n antigen, is present only in\n                    <jats:italic>Helicobacter pylori<\/jats:italic>\n                    strains\n that are associated with severe forms of gastroduodenal disease (type I\n strains). We found that the genetic locus that contains\n                    <jats:italic>cagA<\/jats:italic>\n                    (\n                    <jats:italic>cag<\/jats:italic>\n                    ) is part of a 40-kb DNA\n insertion that likely was acquired horizontally and integrated into the\n chromosomal glutamate racemase gene. This pathogenicity island is\n flanked by direct repeats of 31 bp. In some strains,\n                    <jats:italic>cag<\/jats:italic>\n                    is split into a right segment (\n                    <jats:italic>cag<\/jats:italic>\n                    I) and a left segment\n (\n                    <jats:italic>cag<\/jats:italic>\n                    II) by a novel insertion sequence\n (IS\n                    <jats:italic>605<\/jats:italic>\n                    ). In a minority of\n                    <jats:italic>H. pylori<\/jats:italic>\n                    strains,\n                    <jats:italic>cag<\/jats:italic>\n                    I and\n                    <jats:italic>cag<\/jats:italic>\n                    II are separated by\n an intervening chromosomal sequence. Nucleotide sequencing of the\n 23,508 base pairs that form the\n                    <jats:italic>cag<\/jats:italic>\n                    I region and the\n extreme 3\u2032 end of the\n                    <jats:italic>cag<\/jats:italic>\n                    II region reveals the presence\n of 19 ORFs that code for proteins predicted to be mostly membrane\n associated with one gene (\n                    <jats:italic>cagE<\/jats:italic>\n                    ), which is similar to the\n toxin-secretion gene of\n                    <jats:italic>Bordetella pertussis, ptlC,<\/jats:italic>\n                    and\n the transport systems required for plasmid transfer, including the\n                    <jats:italic>virB4<\/jats:italic>\n                    gene of\n                    <jats:italic>Agrobacterium tumefaciens<\/jats:italic>\n                    .\n Transposon inactivation of several of the\n                    <jats:italic>cag<\/jats:italic>\n                    I genes\n abolishes induction of IL-8 expression in gastric epithelial cell\n lines. Thus, we believe the\n                    <jats:italic>cag<\/jats:italic>\n                    region may encode\n a novel\n                    <jats:italic>H. pylori<\/jats:italic>\n                    secretion system for the export of\n virulence determinants.\n                  <\/jats:p>","DOI":"10.1073\/pnas.93.25.14648","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:43:20Z","timestamp":1027680200000},"page":"14648-14653","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":1495,"title":["<i>cag<\/i>\n                    , a pathogenicity island of\n                    <i>Helicobacter pylori,<\/i>\n                    encodes type I-specific and disease-associated virulence\u2009factors"],"prefix":"10.1073","volume":"93","author":[{"given":"Stefano","family":"Censini","sequence":"first","affiliation":[{"name":"Immunobiological Research Institute of Siena, Chiron Vaccines, Via\r Fiorentina 1, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Lange","sequence":"additional","affiliation":[{"name":"Immunobiological Research Institute of Siena, Chiron Vaccines, Via\r Fiorentina 1, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoying","family":"Xiang","sequence":"additional","affiliation":[{"name":"Immunobiological Research Institute of Siena, Chiron Vaccines, Via\r Fiorentina 1, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2009E.","family":"Crabtree","sequence":"additional","affiliation":[{"name":"Immunobiological Research Institute of Siena, Chiron Vaccines, Via\r Fiorentina 1, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Ghiara","sequence":"additional","affiliation":[{"name":"Immunobiological Research Institute of Siena, Chiron Vaccines, Via\r Fiorentina 1, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Borodovsky","sequence":"additional","affiliation":[{"name":"Immunobiological Research Institute of Siena, Chiron Vaccines, Via\r Fiorentina 1, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rino","family":"Rappuoli","sequence":"additional","affiliation":[{"name":"Immunobiological Research Institute of Siena, Chiron Vaccines, Via\r Fiorentina 1, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonello","family":"Covacci","sequence":"additional","affiliation":[{"name":"Immunobiological Research Institute of Siena, Chiron Vaccines, Via\r Fiorentina 1, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1996,12,10]]},"reference":[{"key":"e_1_3_2_1_2","first-page":"294","volume":"1","author":"Solnick J V","year":"1993","unstructured":"J V Solnick, L S Tompkins Infect Ag Dis 1, 294\u2013309 (1993).","journal-title":"Infect Ag Dis"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199110173251603"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199405053301803"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.63.1.94-98.1995"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/173.5.1171"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.12.5791"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.179.5.1653"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7886456"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.48.1.41"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.47.10.945"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1994.tb00332.x"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.62.6.2609-2613.1994"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.63.5.1681-1687.1995"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.48.10.967"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1992.tb01446.x"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.62.8.3550-3553.1994"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/0882-4010(90)90048-U"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.62.2.606-614.1994"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.5.1664"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.168.1.22-30.1986"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1994.tb00336.x"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1995.mmi_18040715.x"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.6.2593"},{"key":"e_1_3_2_24_2","unstructured":"Akopyants N.\u2009S. Jiang Q. Taylor D.\u2009E. & Berg D.\u2009E.\n (1996) Helicobacter in press."},{"key":"e_1_3_2_25_2","first-page":"726","volume":"10","author":"Stemmer W P C","year":"1991","unstructured":"W P C Stemmer BioTechniques 10, 726 (1991).","journal-title":"BioTechniques"},{"key":"e_1_3_2_26_2","volume-title":"Molecular Cloning: A Laboratory Manual","author":"Maniatis T","year":"1989","unstructured":"T Maniatis, E F Fritsch, J Sambrook Molecular Cloning: A Laboratory Manual (Cold Spring Harbor Lab. Press, 2nd Ed., Plainview, NY, 1989).","edition":"2"},{"key":"e_1_3_2_27_2","volume-title":"Advanced Bacterial Genetics","author":"Davis R H","year":"1980","unstructured":"R H Davis, D Botstein, J R Roth Advanced Bacterial Genetics (Cold Spring Harbor Lab. Press, Plainview, NY, 1980)."},{"key":"e_1_3_2_28_2","volume-title":"Current Protocols in Molecular Biology","author":"Ausubel F M","year":"1987","unstructured":"F M Ausubel, R Brent, R E Kingston, D D Moore, J G Seidman, J A Smith, K Struhl Current Protocols in Molecular Biology (Wiley, New York, Vols. 1\u20133. (1987)."},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/0076-6879(95)54021-0"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.74.12.5463"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/12.1Part1.387"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/22.22.4756"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.175.11.3278-3288.1993"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3083.1993.tb01666.x"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)60637-4"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1993.tb01587.x"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.7.2970"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/0966-842X(96)81513-7"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90146-5"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/141.4.1245"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1119(95)00384-I"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1995.18050867.x"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1119(96)00032-7"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.3.1033"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1993.tb01100.x"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.16.7252"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.148.3.877-883.1981"},{"key":"e_1_3_2_48_2","first-page":"227","volume-title":"Mobile DNA","author":"Kleckner N","year":"1989","unstructured":"N Kleckner Mobile DNA, eds D E Berg, M H Howe (Am. Soc. Microbiol., Washington, DC), pp. 227\u2013268 (1989)."},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/0968-0004(93)90080-7"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/0966-842X(93)90087-8"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.16.6383"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1993.tb06056.x"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90510-X"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.30.17771"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.93.25.14648","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T14:31:43Z","timestamp":1649860303000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.93.25.14648"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1996,12,10]]},"references-count":54,"journal-issue":{"issue":"25","published-print":{"date-parts":[[1996,12,10]]}},"alternative-id":["10.1073\/pnas.93.25.14648"],"URL":"https:\/\/doi.org\/10.1073\/pnas.93.25.14648","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1996,12,10]]},"assertion":[{"value":"1996-06-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"1996-10-09","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"1996-12-10","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}