{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T03:12:59Z","timestamp":1791083579661,"version":"4.1.0"},"reference-count":39,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2017,10,1]],"date-time":"2017-10-01T00:00:00Z","timestamp":1506816000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000057","name":"HHS | NIH | National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["GM068720"],"award-info":[{"award-number":["GM068720"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2017,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:named-content content-type=\"genus-species\">Bacillus anthracis<\/jats:named-content>\n            , the causative agent of anthrax, remains a significant threat to humans, including potential use in bioterrorism and biowarfare. The capacity to engineer strains with increased pathogenicity coupled with the ease of disseminating lethal doses of\n            <jats:named-content content-type=\"genus-species\">B. anthracis<\/jats:named-content>\n            spores makes it necessary to identify chemical agents that target and kill spores. Here, we demonstrate that a tetrazole-based\n            <jats:italic>trans<\/jats:italic>\n            -translation inhibitor, KKL-55, is bactericidal against vegetative cells of\n            <jats:named-content content-type=\"genus-species\">B. anthracis<\/jats:named-content>\n            in culture. Using a fluorescent analog, we show that this class of compounds colocalizes with developing endospores and bind purified spores\n            <jats:italic>in vitro<\/jats:italic>\n            . KKL-55 was effective against spores at concentrations close to its MIC for vegetative cells. Spore germination was inhibited at 1.2\u00d7 MIC, and spores were killed at 2\u00d7 MIC. In contrast, ciprofloxacin killed germinants at concentrations close to its MIC but did not prevent germination even at 32\u00d7 MIC. Because toxins are released by germinants, macrophages infected by\n            <jats:named-content content-type=\"genus-species\">B. anthracis<\/jats:named-content>\n            spores are killed early in the germination process. At \u22652\u00d7 MIC, KKL-55 protected macrophages from death after infection with\n            <jats:named-content content-type=\"genus-species\">B. anthracis<\/jats:named-content>\n            spores. Ciprofloxacin required concentrations of \u22658\u00d7 MIC to exhibit a similar effect. Taken together, these data indicate that KKL-55 and related tetrazoles are good lead candidates for therapeutics targeting\n            <jats:named-content content-type=\"genus-species\">B. anthracis<\/jats:named-content>\n            spores and suggest that there is an early requirement for\n            <jats:italic>trans<\/jats:italic>\n            -translation in germinating spores.\n          <\/jats:p>","DOI":"10.1128\/aac.01199-17","type":"journal-article","created":{"date-parts":[[2017,8,1]],"date-time":"2017-08-01T00:35:13Z","timestamp":1501547713000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":16,"title":["Tetrazole-Based\n            <i>trans<\/i>\n            -Translation Inhibitors Kill Bacillus anthracis Spores To Protect Host Cells"],"prefix":"10.1128","volume":"61","author":[{"given":"John N.","family":"Alumasa","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyler D. P.","family":"Goralski","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth C.","family":"Keiler","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.12998\/wjcc.v3.i1.20"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2221-1691(11)60109-3"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01455-13"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2014.12.019"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2015.01009"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1999.01137.x"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01109-10"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.287.17.2236"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01208-08"},{"key":"e_1_3_2_11_2","volume-title":"Types of anthrax: inhalational anthrax","author":"Centers for Disease Control and Prevention","year":"2017","unstructured":"Centers for Disease Control and Prevention. 2017. Types of anthrax: inhalational anthrax. Centers for Disease Control and Prevention, Atlanta, GA. https:\/\/www.cdc.gov\/anthrax\/basics\/types\/inhalation.html."},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-144-4-200602210-00009"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0810603"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm901024b"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.6.2291"},{"key":"e_1_3_2_16_2","first-page":"335","article-title":"Anthrax: Clinical features, pathogenesis, and potential biological warfare threat","volume":"20","author":"Friedlander AM","year":"2000","unstructured":"Friedlander AM . 2000. Anthrax: Clinical features, pathogenesis, and potential biological warfare threat. 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National Academies Press, Washington, DC."},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.embor.embor860"},{"key":"e_1_3_2_21_2","first-page":"253","volume-title":"The gathering bio-logical warfare storm","author":"Ainscough MJ","year":"2002","unstructured":"Ainscough MJ . 2002. Next generation bioweapons: genetic engineering and bio-logical warfare 9, p 253\u2013288. InDavisJA SchneiderBR (ed), The gathering bio-logical warfare storm, 2nd ed. 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