{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T11:01:49Z","timestamp":1790420509311,"version":"4.1.0"},"reference-count":31,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5517","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2001,4,27]]},"abstract":"<jats:p>The protective antigen moiety of anthrax toxin translocates the toxin's enzymic moieties to the cytosol of mammalian cells by a mechanism that depends on its ability to heptamerize and insert into membranes. We identified dominant-negative mutants of protective antigen that co-assemble with the wild-type protein and block its ability to translocate the enzymic moieties across membranes. These mutants strongly inhibited toxin action in cell culture and in an animal intoxication model, suggesting that they could be useful in therapy of anthrax.<\/jats:p>","DOI":"10.1126\/science.109563","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T05:52:41Z","timestamp":1027749161000},"page":"695-697","source":"Crossref","is-referenced-by-count":157,"title":["Dominant-Negative Mutants of a Toxin Subunit: An Approach to Therapy of Anthrax"],"prefix":"10.1126","volume":"292","author":[{"given":"Bret R.","family":"Sellman","sequence":"first","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Mourez","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"John Collier","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_1_2_2","unstructured":"R. Rapuoli M. Pizza in Cellular Microbiology P. Cossart P. Boquet S. Normark R. Rappuoli Eds. (American Society for Microbiology Press Washington DC 2000) pp. 193\u2013220."},{"key":"e_1_3_1_3_2","doi-asserted-by":"crossref","first-page":"37736","DOI":"10.1074\/jbc.274.53.37736","volume":"274","author":"Vinion-Dubiel A. D.","year":"1999","unstructured":"Vinion-Dubiel A. D., et al., J. Biol. Chem. 274, 37736 (1999).","journal-title":"J. Biol. Chem."},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199909093411107"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.280.5364.734"},{"key":"e_1_3_1_6_2","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1006\/bbrc.1998.9040","volume":"248","author":"Vitale G.","year":"1998","unstructured":"Vitale G., et al., Biochem. Biophys. Res. Commun. 248, 706 (1998).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3520739"},{"key":"e_1_3_1_8_2","unstructured":"J. O'Brien"},{"key":"e_1_3_1_8_3","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1128\/iai.47.1.306-310.1985","volume":"47","author":"Friedlander A.","year":"1985","unstructured":"Friedlander A., Dreier T., Ezzell J., Leppla S., Infect. Immun. 47, 306 (1985).","journal-title":"Infect. Immun."},{"key":"e_1_3_1_9_2","doi-asserted-by":"crossref","first-page":"3381","DOI":"10.1128\/iai.59.10.3381-3386.1991","volume":"59","author":"Escuyer V.","year":"1991","unstructured":"Escuyer V., Collier R. J., Infect. Immun. 59, 3381 (1991).","journal-title":"Infect. Immun."},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.21.10277"},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/385833a0"},{"key":"e_1_3_1_12_2","doi-asserted-by":"crossref","first-page":"20607","DOI":"10.1016\/S0021-9258(17)32036-7","volume":"269","author":"Milne J. C.","year":"1994","unstructured":"Milne J. C., Furlong D., Hanna P. C., Wall J. S., Collier R. J., J. Biol. Chem. 269, 20607 (1994).","journal-title":"J. Biol. Chem."},{"key":"e_1_3_1_13_2","unstructured":"S. H. Leppla in Sourcebook of Bacterial Protein Toxins J. Alouf Ed. (Academic Press New York 1991) pp. 277\u2013302."},{"key":"e_1_3_1_14_2","doi-asserted-by":"crossref","first-page":"6706","DOI":"10.1021\/bi000310u","volume":"39","author":"Elliott J. L.","year":"2000","unstructured":"Elliott J. L., Mogridge J., Collier R. J., Biochemistry 39, 6706 (2000).","journal-title":"Biochemistry"},{"key":"e_1_3_1_15_2","doi-asserted-by":"crossref","first-page":"7123","DOI":"10.1016\/S0021-9258(17)38364-3","volume":"261","author":"Friedlander A. M.","year":"1986","unstructured":"Friedlander A. M., J. Biol. Chem. 261, 7123 (1986).","journal-title":"J. Biol. Chem."},{"key":"e_1_3_1_16_2","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1111\/j.1365-2958.1991.tb00796.x","volume":"5","author":"Koehler T. M.","year":"1991","unstructured":"Koehler T. M., Collier R. J., Mol. Microbiol. 5, 1501 (1991).","journal-title":"Mol. Microbiol."},{"key":"e_1_3_1_17_2","doi-asserted-by":"crossref","first-page":"21782","DOI":"10.1016\/S0021-9258(19)36680-3","volume":"267","author":"Walker B.","year":"1992","unstructured":"Walker B., Krishnasastry M., Zorn L., Bayley H., J. Biol. Chem. 267, 21782 (1992).","journal-title":"J. Biol. Chem."},{"key":"e_1_3_1_18_2","doi-asserted-by":"crossref","first-page":"3941","DOI":"10.1021\/bi972657b","volume":"37","author":"Benson E. L.","year":"1998","unstructured":"Benson E. L., Huynh P. D., Finkelstein A., Collier R. J., Biochemistry 37, 3941 (1998).","journal-title":"Biochemistry"},{"key":"e_1_3_1_19_2","doi-asserted-by":"crossref","first-page":"10432","DOI":"10.1021\/bi990792d","volume":"38","author":"Miller C. J.","year":"1999","unstructured":"Miller C. J., Elliott J. L., Collier R. J., Biochemistry 38, 10432 (1999).","journal-title":"Biochemistry"},{"key":"e_1_3_1_20_2","doi-asserted-by":"crossref","first-page":"8371","DOI":"10.1074\/jbc.M008309200","volume":"276","author":"Sellman B. R.","year":"2001","unstructured":"Sellman B. R., Nassi S., Collier R. J., J. Biol. Chem. 276, 8371 (2001).","journal-title":"J. Biol. Chem."},{"key":"e_1_3_1_21_2","unstructured":"Single-letter abbreviations for the amino acid residues are as follows: A Ala; C Cys; D Asp; E Glu; F Phe; G Gly; H His; I Ile; K Lys; L Leu; M Met; N Asn; P Pro; Q Gln; R Arg; S Ser; T Thr; V Val; W Trp; and Y Tyr."},{"key":"e_1_3_1_22_2","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1111\/j.1365-2958.1995.tb02375.x","volume":"15","author":"Milne J. C.","year":"1995","unstructured":"Milne J. C., Blanke S. R., Hanna P. C., Collier R. J., Mol. Microbiol. 15, 661 (1995).","journal-title":"Mol. Microbiol."},{"key":"e_1_3_1_23_2","doi-asserted-by":"crossref","first-page":"15737","DOI":"10.1021\/bi981436i","volume":"37","author":"Wesche J.","year":"1998","unstructured":"Wesche J., Elliott J. L., Falnes P. O., Olsnes S., Collier R. J., Biochemistry 37, 15737 (1998).","journal-title":"Biochemistry"},{"key":"e_1_3_1_24_2","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1046\/j.1462-5822.2000.00052.x","volume":"2","author":"Beauregard K. E.","year":"2000","unstructured":"Beauregard K. E., Collier R. J., Swanson J. A., Cell. Microbiol. 2, 251 (2000).","journal-title":"Cell. Microbiol."},{"key":"e_1_3_1_25_2","unstructured":"B. R. Sellman M. Mourez R. J. Collier data not shown."},{"key":"e_1_3_1_26_2","doi-asserted-by":"crossref","first-page":"2098","DOI":"10.1128\/aem.55.8.2098-2100.1989","volume":"55","author":"Ivins B. E.","year":"1989","unstructured":"Ivins B. E., Ristroph J. D., Nelson G. O., Appl. Environ. Microbiol. 55, 2098 (1989).","journal-title":"Appl. Environ. Microbiol."},{"key":"e_1_3_1_27_2","doi-asserted-by":"crossref","first-page":"2104","DOI":"10.1001\/jama.282.22.2104","volume":"282","author":"Friedlander A. M.","year":"1999","unstructured":"Friedlander A. M., Pittman P. R., Parker G. W., JAMA 282, 2104 (1999).","journal-title":"JAMA"},{"key":"e_1_3_1_28_2","unstructured":"PA administered with Ribi Tri-Mix adjuvant elicits an anti-PA response and protects animals from challenge by B. anthracis spores (29). We tested the immunogenicity of the double deletion and F427A mutants by vaccinating groups of six male Fisher 344 rats intramuscularly at 0 3 and 6 weeks with each protein (50 \u03bcg) mixed with the Ribi Tri-Mix adjuvant (Sigma) in PBS. The animals were bled prior to the first injection and 14 days following each injection. On day 16 after the final injection the animals were challenged by intravenous injection of a lethal dose of WT-PA plus LF (30 \u03bcg + 6 \u03bcg respectively). Mock-vaccinated animals became moribund 74 min after injection whereas animals vaccinated with any of the DN mutants or with WT-PA survived without symptoms. Titers of PA-reactive and neutralizing antibodies elicited by the DN mutants (measured after the final injection) were greater than or equal to those elicited by WT-PA."},{"key":"e_1_3_1_29_2","unstructured":"Y. Singh H. Kanna A. P. Chopra V. Mehra J. Biol. Chem. in press."},{"key":"e_1_3_1_30_2","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1016\/S0264-410X(97)00268-5","volume":"16","author":"McBride B. W.","year":"1998","unstructured":"McBride B. W., et al., Vaccine 16, 810 (1998).","journal-title":"Vaccine"},{"key":"e_1_3_1_31_2","unstructured":"Supported by grant R37-AI22021 (R.J.C.) and training grant 5T32AI07410 (B.R.S.) from the NIH DSP\/DGA (9860830006) (M.M.) and the Fondation Philippe (M.M.). R.J.C. has financial interest in AVANT Immunotherapeutics Inc."}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.109563","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T23:26:27Z","timestamp":1704842787000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.109563"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,4,27]]},"references-count":31,"journal-issue":{"issue":"5517","published-print":{"date-parts":[[2001,4,27]]}},"alternative-id":["10.1126\/science.109563"],"URL":"https:\/\/doi.org\/10.1126\/science.109563","relation":{},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,4,27]]}}}