{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T11:25:54Z","timestamp":1791199554247,"version":"4.2.0"},"reference-count":34,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2003,5,1]],"date-time":"2003-05-01T00:00:00Z","timestamp":1051747200000},"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":[[2003,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:italic>Tropheryma whipplei<\/jats:italic>\n            , the agent of Whipple's disease, grows fastidiously only in cell cultures without plaque production, and only three strains have been passaged. The formation of bacterial clumps in the supernatant precludes enumeration of viable bacteria and MIC determination. We evaluated the bacteriostatic effects of fluoroquinolones against two\n            <jats:italic>T. whipplei<\/jats:italic>\n            isolates by measuring the inhibition of the DNA copy number increase by real-time quantitative PCR. The analysis of the\n            <jats:italic>T. whipplei<\/jats:italic>\n            genome database allowed the identification not only of the\n            <jats:italic>gyrA<\/jats:italic>\n            gene but also the\n            <jats:italic>parC<\/jats:italic>\n            gene encoding the alpha subunit of the natural fluoroquinolone targets DNA gyrase (GyrA) and topoisomerase IV (ParC), respectively. The\n            <jats:italic>parC<\/jats:italic>\n            gene was detected in actinobacteria for the first time. High ciprofloxacin MICs (4 and 8 \u03bcg\/ml) were correlated with the presence in\n            <jats:italic>T. whipplei<\/jats:italic>\n            GyrA and ParC sequences with an alanine residue at positions 83 and 80 (\n            <jats:italic>Escherichia coli<\/jats:italic>\n            numbering), respectively. Alanines at these positions have previously been associated with increased fluoroquinolone resistance in\n            <jats:italic>E. coli<\/jats:italic>\n            and mycobacteria. However, the MIC of levofloxacin was low (0.25 \u03bcg\/ml). The same\n            <jats:italic>T. whipplei<\/jats:italic>\n            GyrA and ParC sequences were found in two other cultured strains and in nine uncultured tissue samples from Whipple's disease patients, allowing one to speculate that\n            <jats:italic>T. whipplei<\/jats:italic>\n            is naturally relatively resistant to fluoroquinolones.\n          <\/jats:p>","DOI":"10.1128\/aac.47.5.1658-1664.2003","type":"journal-article","created":{"date-parts":[[2003,4,22]],"date-time":"2003-04-22T21:03:23Z","timestamp":1051045403000},"page":"1658-1664","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":56,"title":["Molecular Evaluation of Antibiotic Susceptibility:\n            <i>Tropheryma whipplei<\/i>\n            Paradigm"],"prefix":"10.1128","volume":"47","author":[{"given":"F.","family":"Masselot","sequence":"first","affiliation":[{"name":"Unite\u0301 des Rickettsies, CNRS UMR 6020, Faculte\u0301 de Me\u0301decine, Universite\u0301 de la Me\u0301diterrane\u0301e, 13385 Marseille Cedex 05, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Boulos","sequence":"additional","affiliation":[{"name":"Unite\u0301 des Rickettsies, CNRS UMR 6020, Faculte\u0301 de Me\u0301decine, Universite\u0301 de la Me\u0301diterrane\u0301e, 13385 Marseille Cedex 05, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Maurin","sequence":"additional","affiliation":[{"name":"Unite\u0301 des Rickettsies, CNRS UMR 6020, Faculte\u0301 de Me\u0301decine, Universite\u0301 de la Me\u0301diterrane\u0301e, 13385 Marseille Cedex 05, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. M.","family":"Rolain","sequence":"additional","affiliation":[{"name":"Unite\u0301 des Rickettsies, CNRS UMR 6020, Faculte\u0301 de Me\u0301decine, Universite\u0301 de la Me\u0301diterrane\u0301e, 13385 Marseille Cedex 05, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Raoult","sequence":"additional","affiliation":[{"name":"Unite\u0301 des Rickettsies, CNRS UMR 6020, Faculte\u0301 de Me\u0301decine, Universite\u0301 de la Me\u0301diterrane\u0301e, 13385 Marseille Cedex 05, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/25.17.3389"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.37.12.4189-4191.1999"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1119(94)90628-9"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.33.6.886"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.39.7.2425-2430.2001"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1369-5274(99)00008-9"},{"key":"e_1_3_2_8_2","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1586\/14737159.1.3.299","volume":"1","year":"2001","unstructured":"Fenollar, F., and D. 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