{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T11:25:58Z","timestamp":1791113158473,"version":"4.1.0"},"reference-count":31,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5416","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[1999,5,7]]},"abstract":"<jats:p>\n            <jats:italic>Salmonella typhimurium<\/jats:italic>\n            lacking DNA adenine methylase (Dam) were fully proficient in colonization of mucosal sites but showed severe defects in colonization of deeper tissue sites. These Dam\n            <jats:sup>\u2013<\/jats:sup>\n            mutants were totally avirulent and were effective as live vaccines against murine typhoid fever. Dam regulated the expression of at least 20 genes known to be induced during infection; a subset of these genes are among those activated by the PhoP global virulence regulator. PhoP, in turn, affected Dam methylation at specific genomic sites, as evidenced by alterations in DNA methylation patterns. Dam inhibitors are likely to have broad antimicrobial action, and Dam\n            <jats:sup>\u2013<\/jats:sup>\n            derivatives of these pathogens may serve as live attenuated vaccines.\n          <\/jats:p>","DOI":"10.1126\/science.284.5416.967","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T09:40:50Z","timestamp":1027762850000},"page":"967-970","source":"Crossref","is-referenced-by-count":413,"title":["An Essential Role for DNA Adenine Methylation in Bacterial Virulence"],"prefix":"10.1126","volume":"284","author":[{"given":"Douglas M.","family":"Heithoff","sequence":"first","affiliation":[{"name":"Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, CA 93106, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert L.","family":"Sinsheimer","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, CA 93106, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Low","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, CA 93106, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Mahan","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, CA 93106, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_1_2_2","unstructured":"M. G. Marinus in Escherichia coli and Salmonella : Cellular and Molecular Biology F. Neidhardt Ed. (American Society for Microbiology Washington DC ed. 2 1996) pp. 782\u2013791."},{"key":"e_1_3_1_3_2","doi-asserted-by":"crossref","unstructured":"J. A. Roberts et al. J. Urol. 133 1068 (1985).","DOI":"10.1016\/S0022-5347(17)49382-7"},{"key":"e_1_3_1_4_2","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/0966-842X(96)81498-3","volume":"4","author":"van der Woude M.","year":"1996","unstructured":"van der Woude M., Braaten B., Low D., Trends Microbiol. 4, 5 (1996).","journal-title":"Trends Microbiol."},{"key":"e_1_3_1_5_2","unstructured":"The dam102 ::Mu d -Cm and mutS121 ::Tn 10 alleles (and additional alleles below) were transduced into virulent S. typhimurium strain 14028 resulting in strains MT2116 and MT2127 respectively. dam \u0394 232 (MT2188) was constructed using internal oligonucleotides that serve as polymerase chain reaction primers designed to construct an in-frame 300-bp deletion of defined dam sequence. dcm1 ::Km (MT2198) was constructed according to (26); the Km resistance determinant is associated with an internal deletion of >600 bp of dcm sequence. lrp31 ::Km is a null insertion in the lrp gene (MT2126)."},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.274.5290.1208"},{"key":"e_1_3_1_7_2","unstructured":"E. B. Newman R. T. Lin R. D'Ari in (1) pp. 1513\u20131525."},{"key":"e_1_3_1_8_2","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/0092-8674(94)90120-1","volume":"76","author":"Braaten B. A.","year":"1994","unstructured":"Braaten B. A., Nou X., Kaltenbach L. S., Low D. A., Cell 76, 577 (1994).","journal-title":"Cell"},{"key":"e_1_3_1_9_2","doi-asserted-by":"crossref","unstructured":"D. M. Heithoff et al. Proc. Natl. Acad. Sci. U.S.A. 94 934 (1997).","DOI":"10.1073\/pnas.94.3.934"},{"key":"e_1_3_1_10_2","first-page":"4641","volume":"95","author":"Conner C. P.","year":"1998","unstructured":"Conner C. P., Heithoff D. M., Julio S. M., Sinsheimer R. L., Mahan M. J., ibid. 95, 4641 (1998).","journal-title":"ibid."},{"key":"e_1_3_1_11_2","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1126\/science.8430319","volume":"259","author":"Mahan M. J.","year":"1993","unstructured":"Mahan M. J., Slauch J. M., Mekalanos J. J., Science 259, 666 (1993).","journal-title":"Science"},{"key":"e_1_3_1_12_2","doi-asserted-by":"crossref","unstructured":"M. J. Mahan et al. Proc. Natl. Acad. Sci. U.S.A. 92 669 (1995).","DOI":"10.1073\/pnas.92.3.669"},{"key":"e_1_3_1_13_2","doi-asserted-by":"crossref","unstructured":"P. A. Gulig et al. Mol. Microbiol. 7 825 (1993).","DOI":"10.1111\/j.1365-2958.1993.tb01172.x"},{"key":"e_1_3_1_14_2","doi-asserted-by":"crossref","first-page":"4154","DOI":"10.1128\/jb.175.13.4154-4164.1993","volume":"75","author":"Roland K. L.","year":"1993","unstructured":"Roland K. L., Martin L. E., Esther C. R., Spitznagel J., J. Bacteriol. 75, 4154 (1993).","journal-title":"J. Bacteriol."},{"key":"e_1_3_1_15_2","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/S0092-8674(00)81003-X","volume":"84","author":"Garcia Vescovi E.","year":"1996","unstructured":"Garcia Vescovi E., Soncini F. C., Groisman E. A., Cell 84, 165 (1996).","journal-title":"Cell"},{"key":"e_1_3_1_16_2","unstructured":"C. F. Earhart in (1) pp. 1075\u20131090."},{"key":"e_1_3_1_17_2","unstructured":"E. A. Groisman and F. Heffron in Two-Component Signal Transduction J. A. Hoch and T. J. Silhavy Eds. (American Society for Microbiology Washington DC 1995) pp. 319\u2013332."},{"key":"e_1_3_1_18_2","unstructured":"D. M. Heithoff and M. J. Mahan unpublished data."},{"key":"e_1_3_1_19_2","doi-asserted-by":"crossref","first-page":"5913","DOI":"10.1128\/JB.180.22.5913-5920.1998","volume":"180","author":"van der Woude M.","year":"1998","unstructured":"van der Woude M., Hale W. B., Low D. A., J. Bacteriol. 180, 5913 (1998).","journal-title":"J. Bacteriol."},{"key":"e_1_3_1_20_2","first-page":"3438","volume":"176","author":"Hale W. B.","year":"1994","unstructured":"Hale W. B., van der Woude M. W., Low D. A., ibid. 176, 3438 (1994).","journal-title":"ibid."},{"key":"e_1_3_1_21_2","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1038\/nbt0698-566","volume":"16","author":"Tavazoie S.","year":"1998","unstructured":"Tavazoie S., Church G. M., Nature Biotechnol. 16, 566 (1998).","journal-title":"Nature Biotechnol."},{"key":"e_1_3_1_22_2","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/0378-1119(94)90732-3","volume":"140","author":"Bandyopadhyay R.","year":"1994","unstructured":"Bandyopadhyay R., Das J., Gene 140, 67 (1994).","journal-title":"Gene"},{"key":"e_1_3_1_23_2","unstructured":"Sanger Centre Web site (www.sanger.ac.uk)."},{"key":"e_1_3_1_24_2","doi-asserted-by":"crossref","unstructured":"F. R. Blattner et al. Science 277 1453 (1997).","DOI":"10.1126\/science.277.5331.1453"},{"key":"e_1_3_1_25_2","unstructured":"R. D. Fleischmann et al. ibid. 269 496 (1995)."},{"key":"e_1_3_1_26_2","unstructured":"C. M. Fraser et al. ibid. 281 375 (1998)."},{"key":"e_1_3_1_27_2","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1007\/s004380050721","volume":"258","author":"Julio S. M.","year":"1998","unstructured":"Julio S. M., Conner C. P., Heithoff D. M., Mahan M. J., Mol. Gen. Genet. 258, 178 (1998).","journal-title":"Mol. Gen. Genet."},{"key":"e_1_3_1_28_2","doi-asserted-by":"crossref","unstructured":"D. M. Heithoff et al. J. Bacteriol. 181 799 (1999).","DOI":"10.1128\/JB.181.3.799-807.1999"},{"key":"e_1_3_1_29_2","first-page":"4039","volume":"173","author":"Slauch J. M.","year":"1991","unstructured":"Slauch J. M., Silhavy T., ibid. 173, 4039 (1991).","journal-title":"ibid."},{"key":"e_1_3_1_30_2","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/0076-6879(87)55030-3","volume":"155","author":"Smith C. L.","year":"1987","unstructured":"Smith C. L., Cantor C. R., Methods Enzymol. 155, 449 (1987).","journal-title":"Methods Enzymol."},{"key":"e_1_3_1_31_2","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/0378-1119(84)90095-7","volume":"28","author":"Marinus M. G.","year":"1984","unstructured":"Marinus M. G., Poteete A., Arraj J. A., Gene 28, 123 (1984).","journal-title":"Gene"},{"key":"e_1_3_1_32_2","unstructured":"We thank J. Roth for the dam102 ::Mu d -Cm allele T. Cebula for the mutS121 ::Tn 10 allele R. Ballester for critically reading the manuscript and D. Hillyard for constructing the lrp31 mutant. Supported by NIH grant AI36373 and a Beckman Young Investigator Award (M.J.M.) and NIH grant AI23348 (D.A.L.)."}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.284.5416.967","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,13]],"date-time":"2024-01-13T09:27:10Z","timestamp":1705138030000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.284.5416.967"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,5,7]]},"references-count":31,"journal-issue":{"issue":"5416","published-print":{"date-parts":[[1999,5,7]]}},"alternative-id":["10.1126\/science.284.5416.967"],"URL":"https:\/\/doi.org\/10.1126\/science.284.5416.967","relation":{},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[1999,5,7]]}}}