{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:05:51Z","timestamp":1792785951465,"version":"4.5.0"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2019,10,1]],"date-time":"2019-10-01T00:00:00Z","timestamp":1569888000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Joint Ministerial Program of R&D against CBRNE","award":["NRBC H1.11"],"award-info":[{"award-number":["NRBC H1.11"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,2,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Lethal and edema toxins are critical virulence factors of Bacillus anthracis. Few data are available on their presence in the early stage of intranasal infection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>To investigate the diffusion of edema factor (EF) and lethal factor (LF), we use sensitive quantitative methods to measure their enzymatic activities in mice intranasally challenged with a wild-type B anthracis strain or with an isogenic mutant deficient for the protective antigen.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>One hour after mouse challenge, although only 7% of mice presented bacteremia, LF and EF were detected in the blood of 100% and 42% of mice, respectively. Protective antigen facilitated the diffusion of LF and EF into the blood compartment. Toxins played a significant role in the systemic dissemination of B anthracis in the blood, spleen, and liver. A mouse model of intoxination further confirmed that LT and ET could diffuse rapidly in the circulation, independently of bacteria.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In this inhalational model, toxins have disseminated rapidly in the blood, playing a significant and novel role in the early systemic diffusion of bacteria, demonstrating that they may represent a very early target for the diagnosis and the treatment of anthrax.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/infdis\/jiz497","type":"journal-article","created":{"date-parts":[[2019,9,30]],"date-time":"2019-09-30T23:55:37Z","timestamp":1569887737000},"page":"660-667","source":"Crossref","is-referenced-by-count":13,"title":["Very Early Blood Diffusion of the Active Lethal and Edema Factors of Bacillus anthracis After Intranasal Infection"],"prefix":"10.1093","volume":"221","author":[{"given":"Cl\u00e9mence","family":"Rougeaux","sequence":"first","affiliation":[{"name":"Unit\u00e9 Bioth\u00e9rapies Anti-Infectieuses et Immunit\u00e9, Institut de Recherche Biom\u00e9dicale des Arm\u00e9es, Br\u00e9tigny-sur-Orge, France"},{"name":"Pathog\u00e9nie des Toxi-Infections Bact\u00e9riennes, Institut Pasteur, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"Becher","sequence":"additional","affiliation":[{"name":"Service de Pharmacologie et d\u2019Immunoanalyse, Laboratoire d\u2019Etude du M\u00e9tabolisme des M\u00e9dicaments, Commissariat \u00e0 l\u2019Energie Atomique et aux Energies Alternatives, Institut National de la Recherche Agronomique, Universit\u00e9 Paris Saclay, Gif-sur-Yvette, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre L","family":"Goossens","sequence":"additional","affiliation":[{"name":"Pathog\u00e9nie des Toxi-Infections Bact\u00e9riennes, Institut Pasteur, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Nicolas","family":"Tournier","sequence":"additional","affiliation":[{"name":"Unit\u00e9 Bioth\u00e9rapies Anti-Infectieuses et Immunit\u00e9, Institut de Recherche Biom\u00e9dicale des Arm\u00e9es, Br\u00e9tigny-sur-Orge, France"},{"name":"Pathog\u00e9nie des Toxi-Infections Bact\u00e9riennes, Institut Pasteur, Paris, France"},{"name":"Ecole du Val-de-Gr\u00e2ce, Paris, France"},{"name":"Centre National de R\u00e9f\u00e9rence-Laboratoire Expert Charbon, Institut de Recherche Biom\u00e9dicale des Arm\u00e9es, Br\u00e9tigny-sur-Orge, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,10,1]]},"reference":[{"key":"2020021221371659400_CIT0001","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1056\/NEJM199909093411107","article-title":"Anthrax","volume":"341","author":"Dixon","year":"1999","journal-title":"N Engl J Med"},{"key":"2020021221371659400_CIT0002","doi-asserted-by":"crossref","first-page":"1626","DOI":"10.1128\/IAI.06061-11","article-title":"Updating perspectives on the initiation of Bacillus anthracis growth and dissemination through its host","volume":"80","author":"Weiner","year":"2012","journal-title":"Infect Immun"},{"key":"2020021221371659400_CIT0003","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.3389\/fmicb.2015.01122","article-title":"Crossing of the epithelial barriers by Bacillus anthracis: the known and the unknown","volume":"6","author":"Goossens","year":"2015","journal-title":"Front 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Woolfitt\n              AB\n            , Gallegos-CandelaM, LinsR, et al\n          Development of anthrax toxemia in New Zealand white rabbits developing systemic anthrax after exposure to low-dose ames spores. In: The International Conference on Bacillus anthracis, B cereus and B thuringiensis, Vicotria, British Columbia, Canada, 1\u20135 October 2017."},{"key":"2020021221371659400_CIT0042","unstructured":"A.E. Boyer\n              CPQ\n            , SanfordD, StarkG, et al\n          Toxin levels predict survival with antimicrobial treatment in nonhuman primate models of inhalation anthrax. 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