{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T22:05:07Z","timestamp":1791065107395,"version":"4.1.0"},"reference-count":28,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2004,11,1]],"date-time":"2004-11-01T00:00:00Z","timestamp":1099267200000},"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":["Appl Environ Microbiol"],"published-print":{"date-parts":[[2004,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:italic>Francisella tularensis<\/jats:italic>\n            is a highly virulent zoonotic bacterial pathogen capable of infecting numerous different mammalian species, including humans. Elucidation of the pathogenic mechanisms of\n            <jats:italic>F. tularensis<\/jats:italic>\n            has been hampered by a lack of tools to genetically manipulate this organism. Herein we describe the use of transposome complexes to create insertion mutations in the chromosome of the\n            <jats:italic>F. tularensis<\/jats:italic>\n            live vaccine strain (LVS). A Tn\n            <jats:italic>5<\/jats:italic>\n            -derived transposon encoding kanamycin resistance and lacking a transposase gene was complexed with transposase enzyme and transformed directly into\n            <jats:italic>F. tularensis<\/jats:italic>\n            LVS by electroporation. An insertion frequency of 2.6 \u00d7 10\n            <jats:sup>\u22128<\/jats:sup>\n            \u00b1 0.87 \u00d7 10\n            <jats:sup>\u22128<\/jats:sup>\n            per cell was consistently achieved using this method. There are 178 described Tn\n            <jats:italic>5<\/jats:italic>\n            consensus target sites distributed throughout the\n            <jats:italic>F. tularensis<\/jats:italic>\n            genome. Twenty-two of 26 transposon insertions analyzed were within known or predicted open reading frames, but none of these insertions was associated with the Tn\n            <jats:italic>5<\/jats:italic>\n            target site. Analysis of the insertions of sequentially passed strains indicated that the transposons were maintained stably at the initial insertion site after more than 270 generations. Therefore, transformation by electroporation of Tn\n            <jats:italic>5<\/jats:italic>\n            -based transposon-transposase complexes provided an efficient mechanism for generating random, stable chromosomal insertion mutations in\n            <jats:italic>F. tularensis<\/jats:italic>\n            .\n          <\/jats:p>","DOI":"10.1128\/aem.70.11.6901-6904.2004","type":"journal-article","created":{"date-parts":[[2004,11,4]],"date-time":"2004-11-04T21:58:18Z","timestamp":1099605498000},"page":"6901-6904","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":41,"title":["Use of Transposon-Transposase Complexes To Create Stable Insertion Mutant Strains of\n            <i>Francisella tularensis<\/i>\n            LVS"],"prefix":"10.1128","volume":"70","author":[{"given":"Thomas H.","family":"Kawula","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua D.","family":"Hall","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James R.","family":"Fuller","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin R.","family":"Craven","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1936.02770130028009"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1998.00926.x"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6968.2000.tb08874.x"},{"key":"e_1_3_2_5_2","unstructured":"Cross J. T. and R. L. Penn. 2000. Francisella tularensis (tularemia). Churchill Livingstone Philadelphia Pa."},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.63.4.1478-1483.1995"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005792-192812000-00002"},{"key":"e_1_3_2_8_2","unstructured":"French G. R. 1999. Miscellaneous limited-use vaccines. W. B. Saunders Philadelphia Pa."},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1097(03)00313-6"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/72017"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.18.10716"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6968.2002.tb11369.x"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/0165-2478(94)00158-8"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200111293452211"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.39.9.3140-3146.2001"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1097(03)00820-6"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0307690101"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.60.1.84-89.1992"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.172.10.5956-5960.1990"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1119(85)90021-6"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1945.02860410011003"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.1961.03620010125020"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.1961.03620050068007"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0003-2697(03)00352-X"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-1-12-1007"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1097\/00000441-194508000-00013"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/11.3.440"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF03040310"},{"key":"e_1_3_2_29_2","unstructured":"Wong J. D. and D. S. Shapiro. 1999. Francisella p. 647-651. In P. R. Murray E. J. Baron M. A. Pfaller F. C. Tenover and R. H. Yolken (ed.) Manual of clinical microbiology 7th ed. ASM Press Washington D.C."}],"container-title":["Applied and Environmental Microbiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AEM.70.11.6901-6904.2004","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AEM.70.11.6901-6904.2004","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,23]],"date-time":"2022-02-23T01:51:14Z","timestamp":1645581074000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AEM.70.11.6901-6904.2004"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,11]]},"references-count":28,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2004,11]]}},"alternative-id":["10.1128\/AEM.70.11.6901-6904.2004"],"URL":"https:\/\/doi.org\/10.1128\/aem.70.11.6901-6904.2004","relation":{},"ISSN":["0099-2240","1098-5336"],"issn-type":[{"value":"0099-2240","type":"print"},{"value":"1098-5336","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,11]]},"assertion":[{"value":"2004-03-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2004-06-28","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2004-11-04","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}