{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T13:25:53Z","timestamp":1762867553586},"reference-count":39,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[1999,11,1]],"date-time":"1999-11-01T00:00:00Z","timestamp":941414400000},"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":[[1999,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:italic>Streptococcus pneumoniae<\/jats:italic>\n            topoisomerase IV and DNA gyrase have been purified from a fluoroquinolone-susceptible\n            <jats:italic>Streptococcus pneumoniae<\/jats:italic>\n            strain, from first-step mutants showing low-level resistance to ciprofloxacin, sparfloxacin, levofloxacin, and ofloxacin, and from two clinical isolates showing intermediate- and high-level fluoroquinolone resistance by a gene cloning method that produces recombinant proteins from\n            <jats:italic>Escherichia coli<\/jats:italic>\n            . The concentrations of ciprofloxacin, sparfloxacin, levofloxacin, or ofloxacin required to inhibit wild-type topoisomerase IV were 8 to 16 times lower than those required to inhibit wild-type DNA gyrase. Furthermore, low-level resistance to these fluoroquinolones was entirely due to the reduced inhibitory activity of fluoroquinolones against topoisomerase IV. For all the laboratory strains, the 50% inhibitory concentration for topoisomerase IV directly correlated with the MIC. We therefore propose that with\n            <jats:italic>S. pneumoniae<\/jats:italic>\n            , ciprofloxacin, sparfloxacin, levofloxacin, and ofloxacin target topoisomerase IV in preference to DNA gyrase. Sitafloxacin, on the other hand, was found to be equipotent against either enzyme. This characteristic is unique for a fluoroquinolone. A reduction in the sensitivities of both topoisomerase IV and DNA gyrase are required, however, to achieve intermediate- or high-level fluoroquinolone resistance in\n            <jats:italic>S. pneumoniae<\/jats:italic>\n            .\n          <\/jats:p>","DOI":"10.1128\/aac.43.11.2579","type":"journal-article","created":{"date-parts":[[2018,10,9]],"date-time":"2018-10-09T00:33:39Z","timestamp":1539045219000},"page":"2579-2585","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":49,"title":["Activities of Fluoroquinolones against\n            <i>Streptococcus pneumoniae<\/i>\n            Type II Topoisomerases Purified as Recombinant Proteins"],"prefix":"10.1128","volume":"43","author":[{"given":"Ian","family":"Morrissey","sequence":"first","affiliation":[{"name":"<!--label omitted: 1-->GR Micro Ltd., London NW1 3ER,1 and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"George","sequence":"additional","affiliation":[{"name":"<!--label omitted: 2-->Department of Biosciences, University of Hertfordshire, Hatfield, Herts AL10 9AB,2 United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.180.11.2854-2861.1998"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.40.12.2714"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.1.175"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1996.0274"},{"key":"e_1_3_2_6_2","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/0378-1119(88)90004-2","article-title":"Vectors that facilitate the expression and purification of foreign peptides in Escherichia coli by fusion to the maltose-binding protein.","volume":"67","author":"Diguan C.","year":"1988","unstructured":"Diguan C. Li P. Riggs P. D. Inouye H. Vectors that facilitate the expression and purification of foreign peptides in Escherichia coli by fusion to the maltose-binding protein. Gene 67 1988 21 30","journal-title":"Gene"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/mmbr.61.3.377-392.1997"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1994.tb00458.x"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.39.7.1554"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.73.11.3872"},{"key":"e_1_3_2_11_2","unstructured":"George\n              J. T.\n              Morrissey\n              I.\n          Purification of topoisomerase IV from staphylococcus aureus C3LN4 and inhibition by fluoroquinolones abstr. C-90\n          Program and abstracts of the 37th Interscience Conference on Antimicrobial Agents and Chemotherapy.\n          1997\n          61\n          62\n          American Society for Microbiology\n          Washington D.C."},{"key":"e_1_3_2_12_2","unstructured":"George\n              J. T.\n              Morrissey\n              I.\n          Activity of levofloxacin ofloxacin ciprofloxacin and sparfloxacin against DNA gyrase from S. pneumoniae C3LN4 abstr. C-176\n          Program and abstracts of the 38th Interscience Conference on Antimicrobial Agents and Chemotherapy.\n          1998\n          120\n          American Society for Microbiology\n          Washington D.C."},{"key":"e_1_3_2_13_2","unstructured":"George\n              J. T.\n              Morrissey\n              I.\n          The unique equipotency of sitafloxacin against topoisomerase IV and DNA gyrase from Streptococcus pneumoniae Programme and abstracts of the 6th International Symposium on New Quinolones\n          1998\n          55"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.40.12.2691"},{"key":"e_1_3_2_15_2","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/S0732-8893(96)00135-6","article-title":"Results of the Alexander Project: a continuing, multicenter study of the antimicrobial susceptibility of community-acquired lower respiratory tract bacterial pathogens.","volume":"25","author":"Gr\u00fcneberg R. N.","year":"1996","unstructured":"Gr\u00fcneberg R. N. Felmingham D. the Alexander Project Group Results of the Alexander Project: a continuing, multicenter study of the antimicrobial susceptibility of community-acquired lower respiratory tract bacterial pathogens. Diagn. Microbiol. Infect. Dis. 25 1996 169 181","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.40.4.879"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.38.11.2623"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.14.2.240"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.40.12.2760"},{"key":"e_1_3_2_20_2","unstructured":"Johnson\n              A. P.\n              Stewart\n              B.\n              Woodford\n              N.\n              Warner\n              M.\n          Activity of grepafloxacin against ciprofloxacin-resistant clinical isolates of Streptococcus pneumoniae Programme and abstracts of the 6th International Symposium on New Quinolones\n          1998\n          50"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90172-B"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.25.11801"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.40.3.710"},{"key":"e_1_3_2_24_2","doi-asserted-by":"crossref","first-page":"2252","DOI":"10.1128\/AAC.40.10.2252","article-title":"ParC subunit of topoisomerase IV of Streptococcus pneumoniae is a primary target of fluoroquinolones and cooperates with DNA gyrase A subunit in forming resistance phenotype.","volume":"40","author":"Mu\u00f1oz R.","year":"1996","unstructured":"Mu\u00f1oz R. De La Campa A. G. ParC subunit of topoisomerase IV of Streptococcus pneumoniae is a primary target of fluoroquinolones and cooperates with DNA gyrase A subunit in forming resistance phenotype. Antimicrob. Agents Chemother. 40 1996 2252 2257","journal-title":"Antimicrob. Agents Chemother."},{"key":"e_1_3_2_25_2","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/0076-6879(87)53072-5","article-title":"Synthesis of sequence-specific proteolysis of hybrid protein produced in Escherichia coli.","volume":"153","author":"Nagai K.","year":"1987","unstructured":"Nagai K. Thogersen S. C. Synthesis of sequence-specific proteolysis of hybrid protein produced in Escherichia coli. Methods Enzymol. 153 1987 461 481","journal-title":"Methods Enzymol."},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.33.2.254"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.40.8.1881"},{"key":"e_1_3_2_28_2","unstructured":"Onodera\n              Y.\n              Uchida\n              Y.\n              Tanaka\n              M.\n              Sato\n              K.\n          Dual inhibitory activity of DU-6859a against DNA gyrase and topoisomerase IV of Streptococcus pneumoniae abstr. C-175\n          Program and abstracts of the 38th Interscience Conference on Antimicrobial Agents and Chemotherapy.\n          1998\n          119\n          American Society for Microbiology\n          Washington D.C."},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.40.10.2321"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.178.14.4060-4069.1996"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.2.471"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.11.2810"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.5.1166"},{"key":"e_1_3_2_34_2","first-page":"299","article-title":"Awakening the slumbering potential of the 4-quinolone antibacterials.","volume":"233","author":"Smith J. T.","year":"1984","unstructured":"Smith J. T. Awakening the slumbering potential of the 4-quinolone antibacterials. Pharm. J. 233 1984 299 305","journal-title":"Pharm. 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