{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T18:16:53Z","timestamp":1763662613933},"reference-count":42,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2006,8,1]],"date-time":"2006-08-01T00:00:00Z","timestamp":1154390400000},"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":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2006,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:italic>Bacillus anthracis<\/jats:italic>\n            lethal toxin (LT) produces symptoms of anthrax in mice and induces rapid lysis of macrophages derived from certain inbred strains. LT is comprised of a receptor binding component, protective antigen (PA), which delivers the enzymatic component, lethal factor (LF), into cells. We found that mouse macrophages were protected from toxin by the antitumor drug\n            <jats:italic>cis<\/jats:italic>\n            -diammineplatinum (II) dichloride (cisplatin). Cisplatin was shown to inhibit LT-mediated cleavage of cellular mitogen-activated protein kinases (MEKs) without inhibiting LF's in vitro proteolytic activity. Cisplatin-treated PA lost 100% of its ability to function in toxicity assays when paired with untreated LF, despite maintaining the ability to bind to cells. Cisplatin-treated PA was unable to form heptameric oligomers required for LF binding and translocation. The drug was shown to modify PA in a reversible noncovalent manner. Not surprisingly, cisplatin also blocked the actions of anthrax edema toxin and of LF-\n            <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n            exotoxin A fusion peptide (FP59), both of which require PA for translocation. Treatment of BALB\/cJ mice or Fischer F344 rats with cisplatin at biologically relevant concentrations completely protected the animals from a coadministered lethal dose of LT. However, treatment with cisplatin 2 hours before or after animals received a lethal bolus of toxin did not protect them.\n          <\/jats:p>","DOI":"10.1128\/aac.01412-05","type":"journal-article","created":{"date-parts":[[2006,7,26]],"date-time":"2006-07-26T18:17:58Z","timestamp":1153937878000},"page":"2658-2665","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":30,"title":["Cisplatin Inhibition of Anthrax Lethal Toxin"],"prefix":"10.1128","volume":"50","author":[{"given":"Mahtab","family":"Moayeri","sequence":"first","affiliation":[{"name":"Bacterial Toxins and Therapeutics Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason F.","family":"Wiggins","sequence":"additional","affiliation":[{"name":"Bacterial Toxins and Therapeutics Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robin E.","family":"Lindeman","sequence":"additional","affiliation":[{"name":"Bacterial Toxins and Therapeutics Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen H.","family":"Leppla","sequence":"additional","affiliation":[{"name":"Bacterial Toxins and Therapeutics Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","first-page":"363","year":"1999","unstructured":"Appleton, T. 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