{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:29:03Z","timestamp":1787016543650,"version":"build-2736575974"},"reference-count":45,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2012,5,1]],"date-time":"2012-05-01T00:00:00Z","timestamp":1335830400000},"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":[[2012,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    TP-434 is a novel, broad-spectrum fluorocycline antibiotic with activity against bacteria expressing major antibiotic resistance mechanisms, including tetracycline-specific efflux and ribosomal protection. The mechanism of action of TP-434 was assessed using both cell-based and\n                    <jats:italic>in vitro<\/jats:italic>\n                    assays. In\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Escherichia coli<\/jats:named-content>\n                    cells expressing recombinant tetracycline resistance genes, the MIC of TP-434 (0.063 \u03bcg\/ml) was unaffected by\n                    <jats:italic>tet<\/jats:italic>\n                    (M),\n                    <jats:italic>tet<\/jats:italic>\n                    (K), and\n                    <jats:italic>tet<\/jats:italic>\n                    (B) and increased to 0.25 and 4 \u03bcg\/ml in the presence of\n                    <jats:italic>tet<\/jats:italic>\n                    (A) and\n                    <jats:italic>tet<\/jats:italic>\n                    (X), respectively. Tetracycline, in contrast, was significantly less potent (MIC \u2265 128 \u03bcg\/ml) against\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">E. coli<\/jats:named-content>\n                    cells when any of these resistance mechanisms were present. TP-434 showed potent inhibition in\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">E. coli in vitro<\/jats:named-content>\n                    transcription\/translation (50% inhibitory concentration [IC\n                    <jats:sub>50<\/jats:sub>\n                    ] = 0.29 \u00b1 0.09 \u03bcg\/ml) and [\n                    <jats:sup>3<\/jats:sup>\n                    H]tetracycline ribosome-binding competition (IC\n                    <jats:sub>50<\/jats:sub>\n                    = 0.22 \u00b1 0.07 \u03bcM) assays. The antibacterial potencies of TP-434 and all other tetracycline class antibiotics tested were reduced by 4- to 16-fold, compared to that of the wild-type control strain, against\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Propionibacterium acnes<\/jats:named-content>\n                    strains carrying a 16S rRNA mutation, G1058C, a modification that changes the conformation of the primary binding site of tetracycline in the ribosome. Taken together, the findings support the idea that TP-434, like other tetracyclines, binds the ribosome and inhibits protein synthesis and that this activity is largely unaffected by the common tetracycline resistance mechanisms.\n                  <\/jats:p>","DOI":"10.1128\/aac.06187-11","type":"journal-article","created":{"date-parts":[[2012,2,21]],"date-time":"2012-02-21T21:37:05Z","timestamp":1329860225000},"page":"2559-2564","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":155,"title":["Target- and Resistance-Based Mechanistic Studies with TP-434, a Novel Fluorocycline Antibiotic"],"prefix":"10.1128","volume":"56","author":[{"given":"Trudy H.","family":"Grossman","sequence":"first","affiliation":[{"name":"Tetraphase Pharmaceuticals, Inc., Watertown, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agata L.","family":"Starosta","sequence":"additional","affiliation":[{"name":"Gene Center, Department of Biochemistry, University of Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corey","family":"Fyfe","sequence":"additional","affiliation":[{"name":"Tetraphase Pharmaceuticals, Inc., Watertown, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"O'Brien","sequence":"additional","affiliation":[{"name":"Tetraphase Pharmaceuticals, Inc., Watertown, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Rothstein","sequence":"additional","affiliation":[{"name":"Tetraphase Pharmaceuticals, Inc., Watertown, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Mikolajka","sequence":"additional","affiliation":[{"name":"Gene Center, Department of Biochemistry, University of Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel N.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Gene Center, Department of Biochemistry, University of Munich, Germany"},{"name":"Center for Integrated Protein Science Munich (CiPSM), University of Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joyce A.","family":"Sutcliffe","sequence":"additional","affiliation":[{"name":"Tetraphase Pharmaceuticals, Inc., Watertown, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkh125"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.40.9.2226"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)00216-6"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.70.4.2503-2507.2004"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.178.11.3246-3251.1996"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/ja.2011.44"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1109755"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm201467r"},{"key":"e_1_3_1_10_2","volume-title":"CLSI document M07-A8","author":"Clinical and Laboratory Standards Institute (CLSI)","year":"2009","unstructured":"Clinical and Laboratory Standards Institute (CLSI). 2009. 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