{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T12:51:11Z","timestamp":1790513471519,"version":"4.1.0"},"reference-count":40,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2018,1,1]],"date-time":"2018-01-01T00:00:00Z","timestamp":1514764800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Microbial Drug Resistance"],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:p>\n                    High-level fluoroquinolone resistance is conferred by the mutation of conserved serine and acidic amino acids in the quinolone resistance-determining region (QRDR) of the A subunits of the type II topoisomerases, DNA gyrase (GyrA) and topoisomerase IV (ParC). In Japan, fluoroquinolone-resistant\n                    <jats:italic toggle=\"yes\">Enterococcus faecium<\/jats:italic>\n                    continues to emerge in clinical settings. We analyzed 131 Japanese\n                    <jats:italic toggle=\"yes\">E<\/jats:italic>\n                    .\n                    <jats:italic toggle=\"yes\">faecium<\/jats:italic>\n                    clinical isolates for susceptibility to levofloxacin (LVFX), and QRDR mutational status. The bacterial collection had a high percentage of resistance (79%) and showed elevated drug minimal inhibitory concentrations (MICs). Eighty-three isolates had single or combined mutations in\n                    <jats:italic toggle=\"yes\">gyrA<\/jats:italic>\n                    and\/or\n                    <jats:italic toggle=\"yes\">parC<\/jats:italic>\n                    ; all were resistant to LVFX. A strong correlation was evident between log-transformed MICs and the total number of QRDR mutations (\n                    <jats:italic toggle=\"yes\">r<\/jats:italic>\n                    \u2009=\u20090.7899), confirming the involvement of QRDR mutations in drug resistance, as previously described. Three-dimensional modeling indicated that the amino acid change(s) in QRDR could disrupt the interaction between the enzymes and drugs: the most common cause of quinolone resistance. Interestingly, eight isolates had a single mutation on\n                    <jats:italic toggle=\"yes\">gyrA<\/jats:italic>\n                    and exhibited significantly reduced susceptibility. These data imply that either DNA gyrase or topoisomerase IV can be the primary target of fluoroquinolones, although topoisomerase IV is commonly thought to be the primary target in gram-positive bacteria.\n                  <\/jats:p>","DOI":"10.1089\/mdr.2016.0328","type":"journal-article","created":{"date-parts":[[2017,5,15]],"date-time":"2017-05-15T14:54:54Z","timestamp":1494860094000},"page":"1-7","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":7,"title":["Contribution of Type II Topoisomerase Mutations to Fluoroquinolone Resistance in\n                    <i>Enterococcus faecium<\/i>\n                    from Japanese Clinical Setting"],"prefix":"10.1177","volume":"24","author":[{"given":"Noriko","family":"Urushibara","sequence":"first","affiliation":[{"name":"Sapporo Medical University School of Medicine","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keisuke","family":"Suzaki","sequence":"additional","affiliation":[{"name":"Sapporo Medical University School of Medicine","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuyo","family":"Kawaguchiya","sequence":"additional","affiliation":[{"name":"Sapporo Medical University School of Medicine","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meiji Soe","family":"Aung","sequence":"additional","affiliation":[{"name":"Sapporo Medical University School of Medicine","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaaki","family":"Shinagawa","sequence":"additional","affiliation":[{"name":"Sapporo Medical University Hospital","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Sapporo Medical University School of Medicine","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobumichi","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Sapporo Medical University School of Medicine","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2018,1]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.12830"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2014.04.007"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.2174\/156802609789630947"},{"key":"e_1_3_3_5_2","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1128\/AAC.01617-06","article-title":"Quinolone-mediated bacterial death","volume":"52","author":"Drlica K.","year":"2008","unstructured":"Drlica K., , Malik M., , Kerns R.J., , and Zhao X.. 2008. Quinolone-mediated bacterial death. Antimicrob. Agents Chemother., 52:385\u2013392.","journal-title":"Antimicrob. Agents Chemother."},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1086\/428052"},{"key":"e_1_3_3_7_2","first-page":"337","article-title":"Type II topoisomerases as targets for quinolone antibacterials: turning Dr","volume":"7","author":"Anderson V.E.","year":"2001","unstructured":"Anderson V.E., , and Osheroff N.. 2001. Type II topoisomerases as targets for quinolone antibacterials: turning Dr. Jekyll into Mr. Hyde. Curr. Pharm. Des., 7:337\u2013353.","journal-title":"Jekyll into Mr. Hyde. Curr. Pharm. 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