{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T19:32:53Z","timestamp":1791142373436,"version":"4.1.0"},"reference-count":61,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2011,7,1]],"date-time":"2011-07-01T00:00:00Z","timestamp":1309478400000},"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":["Infect Immun"],"published-print":{"date-parts":[[2011,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Bacillus anthracis<\/jats:named-content>\n            is a Gram-positive spore-forming bacterium that causes anthrax disease in humans and animals. Systemic infection is characterized by septicemia, toxemia, and meningitis, the main neurological complication associated with high mortality. We have shown previously that\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">B. anthracis<\/jats:named-content>\n            Sterne is capable of blood-brain barrier (BBB) penetration, establishing the classic signs of meningitis, and that infection is dependent on the expression of both major anthrax toxins, lethal toxin (LT) and edema toxin (ET). Here we further investigate the contribution of the individual toxins to BBB disruption using isogenic toxin mutants deficient in lethal factor, \u0394LF, and edema factor, \u0394EF. Acute infection with\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">B. anthracis<\/jats:named-content>\n            Sterne and the \u0394LF mutant resulted in disruption of human brain microvascular endothelial cell (hBMEC) monolayer integrity and tight junction protein zona occludens-1, while the result for cells infected with the \u0394EF mutant was similar to that for the noninfected control. A significant decrease in bacterial invasion of BBB endothelium\n            <jats:italic>in vitro<\/jats:italic>\n            was observed during infection with the \u0394LF strain, suggesting a prominent role for LT in promoting BBB interaction. Further, treatment of hBMECs with purified LT or chemicals that mimic LT action on host signaling pathways rescued the hypoinvasive phenotype of the \u0394LF mutant and resulted in increased bacterial uptake. We also observed that toxin expression reduced bacterial intracellular survival by inducing the bulk degradative autophagy pathway in host cells. Finally, in a murine model of anthrax meningitis, mice infected with the \u0394LF mutant exhibited no mortality, brain bacterial load, or evidence of meningitis compared to mice infected with the parental or \u0394EF strains.\n          <\/jats:p>","DOI":"10.1128\/iai.00006-11","type":"journal-article","created":{"date-parts":[[2011,4,26]],"date-time":"2011-04-26T02:39:56Z","timestamp":1303785596000},"page":"2510-2518","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":43,"title":["Contribution of Lethal Toxin and Edema Toxin to the Pathogenesis of Anthrax Meningitis"],"prefix":"10.1128","volume":"79","author":[{"given":"Celia M.","family":"Ebrahimi","sequence":"first","affiliation":[{"name":"Department of Biology and Center for Microbial Sciences, San Diego State University, 5500 Campanile Dr., San Diego, California 92182"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamsin R.","family":"Sheen","sequence":"additional","affiliation":[{"name":"Department of Biology and Center for Microbial Sciences, San Diego State University, 5500 Campanile Dr., San Diego, California 92182"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian W.","family":"Renken","sequence":"additional","affiliation":[{"name":"Applied BioPhysics, Inc. Troy, New York 12180"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta A.","family":"Gottlieb","sequence":"additional","affiliation":[{"name":"Department of Biology and Center for Microbial Sciences, San Diego State University, 5500 Campanile Dr., San Diego, California 92182"},{"name":"BioScience Center, San Diego State University, 5500 Campanile Dr., San Diego, California 92182"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly S.","family":"Doran","sequence":"additional","affiliation":[{"name":"Department of Biology and Center for Microbial Sciences, San Diego State University, 5500 Campanile Dr., San Diego, California 92182"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.6.2291"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01794"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2003.12.016"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj20031382"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/116.3.377"},{"key":"e_1_3_2_7_2","first-page":"2614","article-title":"Epithelial properties of brain capillary endothelium","volume":"44","author":"Betz A. 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