{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T04:11:56Z","timestamp":1791000716144,"version":"4.1.0"},"reference-count":45,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2018,4,1]],"date-time":"2018-04-01T00:00:00Z","timestamp":1522540800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"German Center of Infection Research","award":["TTU 09.902"],"award-info":[{"award-number":["TTU 09.902"]}]},{"name":"German Center of Infection Research","award":["TTU 09.807"],"award-info":[{"award-number":["TTU 09.807"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Scrub typhus is a potentially lethal infection caused by the obligate intracellular bacterium\n            <jats:named-content content-type=\"genus-species\">Orientia tsutsugamushi<\/jats:named-content>\n            . Reports on the emergence of doxycycline-resistant strains highlight the urgent need to develop novel antiinfectives against scrub typhus. Corallopyronin A (CorA) is a novel \u03b1-pyrone compound synthesized by the myxobacterium\n            <jats:named-content content-type=\"genus-species\">Corallococcus coralloides<\/jats:named-content>\n            that was characterized as a noncompetitive inhibitor of the switch region of the bacterial RNA polymerase (RNAP). We investigated the antimicrobial action of CorA against the human-pathogenic Karp strain of\n            <jats:named-content content-type=\"genus-species\">O. tsutsugamushi<\/jats:named-content>\n            <jats:italic>in vitro<\/jats:italic>\n            and\n            <jats:italic>in vivo<\/jats:italic>\n            . The MIC of CorA against\n            <jats:named-content content-type=\"genus-species\">O. tsutsugamushi<\/jats:named-content>\n            was remarkably low (0.0078 \u03bcg\/ml), 16-fold lower than that against\n            <jats:named-content content-type=\"genus-species\">Rickettsia typhi<\/jats:named-content>\n            . In the lethal intraperitoneal\n            <jats:named-content content-type=\"genus-species\">O. tsutsugamushi<\/jats:named-content>\n            mouse infection model, a minimum daily dose of 100 \u03bcg CorA protected 100% of infected mice. Two days of treatment were sufficient to confer protection. In contrast to BALB\/c mice, SCID mice succumbed to the infection despite treatment with CorA or tetracycline, suggesting that antimicrobial treatment required synergistic action of the adaptive immune response. Similar to tetracycline, CorA did not prevent latent infection of\n            <jats:named-content content-type=\"genus-species\">O. tsutsugamushi<\/jats:named-content>\n            <jats:italic>in vivo<\/jats:italic>\n            . However, latency was not caused by acquisition of antimicrobial resistance, since\n            <jats:named-content content-type=\"genus-species\">O. tsutsugamushi<\/jats:named-content>\n            reisolated from latently infected BALB\/c mice remained fully susceptible to CorA. No mutations were found in the CorA-binding regions of the \u03b2 and \u03b2\u2032 RNAP subunit genes\n            <jats:italic>rpoB<\/jats:italic>\n            and\n            <jats:italic>rpoC<\/jats:italic>\n            . Inhibition of the RNAP switch region of\n            <jats:named-content content-type=\"genus-species\">O. tsutsugamushi<\/jats:named-content>\n            by CorA is therefore a novel and highly potent target for antimicrobial therapy for scrub typhus.\n          <\/jats:p>","DOI":"10.1128\/aac.01732-17","type":"journal-article","created":{"date-parts":[[2018,1,18]],"date-time":"2018-01-18T11:28:59Z","timestamp":1516274939000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":26,"title":["Orientia tsutsugamushi Is Highly Susceptible to the RNA Polymerase Switch Region Inhibitor Corallopyronin A\n            <i>In Vitro<\/i>\n            and\n            <i>In Vivo<\/i>"],"prefix":"10.1128","volume":"62","author":[{"given":"Fredericke","family":"Kock","sequence":"first","affiliation":[{"name":"Department of Immunology, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany"},{"name":"German Center for Infection Research (DZIF) Partner Site Hamburg\/L\u00fcbeck\/Borstel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Hauptmann","sequence":"additional","affiliation":[{"name":"Department of Immunology, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany"},{"name":"German Center for Infection Research (DZIF) Partner Site Hamburg\/L\u00fcbeck\/Borstel, Germany"},{"name":"Priority Area Infections, Research Center Borstel, Borstel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anke","family":"Osterloh","sequence":"additional","affiliation":[{"name":"Department of Immunology, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Till F.","family":"Sch\u00e4berle","sequence":"additional","affiliation":[{"name":"Institute for Pharmaceutical Biology, University of Bonn, Bonn, Germany"},{"name":"German Center for Infection Research (DZIF) Partner Site Bonn\/Cologne, Germany"},{"name":"Institute for Insect Biotechnology, Justus Liebig University Giessen, Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4873-249X","authenticated-orcid":false,"given":"Sven","family":"Poppert","sequence":"additional","affiliation":[{"name":"Swiss Tropical and Public Health Institute, Basel, Switzerland"},{"name":"University Basel, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hagen","family":"Frickmann","sequence":"additional","affiliation":[{"name":"Department of Tropical Medicine at the Bernhard Nocht Institute, Bundeswehr Hospital Hamburg, Hamburg, Germany"},{"name":"Institute for Medical Microbiology, Virology and Hygiene, University Medicine Rostock, Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus-Dieter","family":"Menzel","sequence":"additional","affiliation":[{"name":"Bio Pilot Plant, 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