Fluoroquinolone resistance in clinical isolates of Streptococcus pneumoniae : Contributions of type II topoisomerase mutations and efflux to levels of resistance
We report on amino acid substitutions in the quinolone resistance-determining region of type II topisomerases and the prevalence of reserpine-inhibited efflux for 70 clinical isolates of S. pneumoniae for which the ciprofloxacin MIC is >/=4 microgram/ml and 28 isolates for which the ciprofloxacin...
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| Veröffentlicht in: | Antimicrobial agents and chemotherapy 2000-11, Vol.44 (11), p.3049-3054 |
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| creator | BAST, Darrin J LOW, Donald E DUNCAN, Carla L KILBURN, Laurie MANDELL, Lionel A DAVIDSON, Ross J DE AZAVEDO, Joyce C. S |
| description | We report on amino acid substitutions in the quinolone resistance-determining region of type II topisomerases and the prevalence of reserpine-inhibited efflux for 70 clinical isolates of S. pneumoniae for which the ciprofloxacin MIC is >/=4 microgram/ml and 28 isolates for which the ciprofloxacin MIC is |
| doi_str_mv | 10.1128/AAC.44.11.3049-3054.2000 |
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S</creator><creatorcontrib>BAST, Darrin J ; LOW, Donald E ; DUNCAN, Carla L ; KILBURN, Laurie ; MANDELL, Lionel A ; DAVIDSON, Ross J ; DE AZAVEDO, Joyce C. S</creatorcontrib><description>We report on amino acid substitutions in the quinolone resistance-determining region of type II topisomerases and the prevalence of reserpine-inhibited efflux for 70 clinical isolates of S. pneumoniae for which the ciprofloxacin MIC is >/=4 microgram/ml and 28 isolates for which the ciprofloxacin MIC is </=2 microgram/ml. The amino acid substitutions in ParC conferring low-level resistance (MICs, 4 to 8 microgram/ml) included Phe, Tyr, and Ala for Ser-79; Asn, Ala, Gly, Tyr, and Val for Asp-83; Asn for Asp-78; and Pro for Ala-115. Isolates with intermediate-level (MICs, 16 to 32 microgram/ml) and high-level (MICs, 64 microgram/ml) resistance harbored substitutions of Phe and Tyr for Ser-79 or Asn and Ala for Asp-83 in ParC and an additional substitution in GyrA which included either Glu-85-Lys (Gly) or Ser-81-Phe (Tyr). Glu-85-Lys was found exclusively in isolates with high-level resistance. Efflux contributed primarily to low-level resistance in isolates with or without an amino acid substitution in ParC. The impact of amino acid substitutions in ParE was minimal, and no substitutions in GyrB were identified.</description><identifier>ISSN: 0066-4804</identifier><identifier>EISSN: 1098-6596</identifier><identifier>DOI: 10.1128/AAC.44.11.3049-3054.2000</identifier><identifier>PMID: 11036021</identifier><identifier>CODEN: AACHAX</identifier><language>eng</language><publisher>Washington, DC: American Society for Microbiology</publisher><subject>Amino Acid Substitution ; Anti-Infective Agents - pharmacology ; Antibacterial agents ; Antibiotics. Antiinfectious agents. Antiparasitic agents ; Bacterial Proteins - genetics ; Bacterial Proteins - physiology ; Biological and medical sciences ; Biological Transport, Active ; Ciprofloxacin - pharmacology ; DNA Gyrase ; DNA Topoisomerase IV ; DNA Topoisomerases, Type II - genetics ; DNA Topoisomerases, Type II - physiology ; DNA-Binding Proteins - genetics ; DNA-Binding Proteins - physiology ; Drug Resistance, Microbial - genetics ; GyrA protein ; Humans ; Mechanisms of Resistance ; Medical sciences ; Microbial Sensitivity Tests ; ParC protein ; Pharmacology. 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S</creatorcontrib><title>Fluoroquinolone resistance in clinical isolates of Streptococcus pneumoniae : Contributions of type II topoisomerase mutations and efflux to levels of resistance</title><title>Antimicrobial agents and chemotherapy</title><addtitle>Antimicrob Agents Chemother</addtitle><description>We report on amino acid substitutions in the quinolone resistance-determining region of type II topisomerases and the prevalence of reserpine-inhibited efflux for 70 clinical isolates of S. pneumoniae for which the ciprofloxacin MIC is >/=4 microgram/ml and 28 isolates for which the ciprofloxacin MIC is </=2 microgram/ml. The amino acid substitutions in ParC conferring low-level resistance (MICs, 4 to 8 microgram/ml) included Phe, Tyr, and Ala for Ser-79; Asn, Ala, Gly, Tyr, and Val for Asp-83; Asn for Asp-78; and Pro for Ala-115. Isolates with intermediate-level (MICs, 16 to 32 microgram/ml) and high-level (MICs, 64 microgram/ml) resistance harbored substitutions of Phe and Tyr for Ser-79 or Asn and Ala for Asp-83 in ParC and an additional substitution in GyrA which included either Glu-85-Lys (Gly) or Ser-81-Phe (Tyr). Glu-85-Lys was found exclusively in isolates with high-level resistance. Efflux contributed primarily to low-level resistance in isolates with or without an amino acid substitution in ParC. The impact of amino acid substitutions in ParE was minimal, and no substitutions in GyrB were identified.</description><subject>Amino Acid Substitution</subject><subject>Anti-Infective Agents - pharmacology</subject><subject>Antibacterial agents</subject><subject>Antibiotics. Antiinfectious agents. Antiparasitic agents</subject><subject>Bacterial Proteins - genetics</subject><subject>Bacterial Proteins - physiology</subject><subject>Biological and medical sciences</subject><subject>Biological Transport, Active</subject><subject>Ciprofloxacin - pharmacology</subject><subject>DNA Gyrase</subject><subject>DNA Topoisomerase IV</subject><subject>DNA Topoisomerases, Type II - genetics</subject><subject>DNA Topoisomerases, Type II - physiology</subject><subject>DNA-Binding Proteins - genetics</subject><subject>DNA-Binding Proteins - physiology</subject><subject>Drug Resistance, Microbial - genetics</subject><subject>GyrA protein</subject><subject>Humans</subject><subject>Mechanisms of Resistance</subject><subject>Medical sciences</subject><subject>Microbial Sensitivity Tests</subject><subject>ParC protein</subject><subject>Pharmacology. Drug treatments</subject><subject>Phenotype</subject><subject>Streptococcus pneumoniae</subject><subject>Streptococcus pneumoniae - drug effects</subject><subject>Streptococcus pneumoniae - enzymology</subject><subject>Streptococcus pneumoniae - genetics</subject><issn>0066-4804</issn><issn>1098-6596</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkcGOFCEQhonRuOPqKxgOxluP0EB3Y-JhMnF1kk08qGfCQLViaGiB3riP45tK70wcPVFJfT8U9SGEKdlS2g5vdrv9lvNabxnhsmFE8G1LCHmENpTIoemE7B6jDSFd1_CB8Cv0LOcfFagN8hRdUUpYR1q6Qb9v_BJT_Lm4EH0MgBNkl4sOBrAL2HgXnNEeuxy9LpBxHPHnkmAu0URjloznAMsUg9OA3-J9DCW541JcDA9suZ8BHw64xDnWOyZIOgOelqJPiA4Wwzj65VdFsIc78A-5yxjP0ZNR-wwvzuc1-nrz_sv-Y3P76cNhv7ttDO9Faaw0vSYD0cNArbQjb3vobEtHwejQEyag19YIy6RsWW0ZI452oLKjlrbHsWfX6N3p3nk5TmAN1J9or-bkJp3uVdRO_d8J7rv6Fu8UJbQjtOZfn_PrOiEXNblswHsdIC5Z0b7jVEpWweEEmhRzTjD-fYMStepVVa_ivNZq1atWvWrVW6Mv_53xEjz7rMCrM6Bz1TamukGXL5xgohWE_QHTp7PG</recordid><startdate>20001101</startdate><enddate>20001101</enddate><creator>BAST, Darrin J</creator><creator>LOW, Donald E</creator><creator>DUNCAN, Carla L</creator><creator>KILBURN, Laurie</creator><creator>MANDELL, Lionel A</creator><creator>DAVIDSON, Ross J</creator><creator>DE AZAVEDO, Joyce C. 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Antiparasitic agents</topic><topic>Bacterial Proteins - genetics</topic><topic>Bacterial Proteins - physiology</topic><topic>Biological and medical sciences</topic><topic>Biological Transport, Active</topic><topic>Ciprofloxacin - pharmacology</topic><topic>DNA Gyrase</topic><topic>DNA Topoisomerase IV</topic><topic>DNA Topoisomerases, Type II - genetics</topic><topic>DNA Topoisomerases, Type II - physiology</topic><topic>DNA-Binding Proteins - genetics</topic><topic>DNA-Binding Proteins - physiology</topic><topic>Drug Resistance, Microbial - genetics</topic><topic>GyrA protein</topic><topic>Humans</topic><topic>Mechanisms of Resistance</topic><topic>Medical sciences</topic><topic>Microbial Sensitivity Tests</topic><topic>ParC protein</topic><topic>Pharmacology. 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S</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Fluoroquinolone resistance in clinical isolates of Streptococcus pneumoniae : Contributions of type II topoisomerase mutations and efflux to levels of resistance</atitle><jtitle>Antimicrobial agents and chemotherapy</jtitle><addtitle>Antimicrob Agents Chemother</addtitle><date>2000-11-01</date><risdate>2000</risdate><volume>44</volume><issue>11</issue><spage>3049</spage><epage>3054</epage><pages>3049-3054</pages><issn>0066-4804</issn><eissn>1098-6596</eissn><coden>AACHAX</coden><abstract>We report on amino acid substitutions in the quinolone resistance-determining region of type II topisomerases and the prevalence of reserpine-inhibited efflux for 70 clinical isolates of S. pneumoniae for which the ciprofloxacin MIC is >/=4 microgram/ml and 28 isolates for which the ciprofloxacin MIC is </=2 microgram/ml. The amino acid substitutions in ParC conferring low-level resistance (MICs, 4 to 8 microgram/ml) included Phe, Tyr, and Ala for Ser-79; Asn, Ala, Gly, Tyr, and Val for Asp-83; Asn for Asp-78; and Pro for Ala-115. Isolates with intermediate-level (MICs, 16 to 32 microgram/ml) and high-level (MICs, 64 microgram/ml) resistance harbored substitutions of Phe and Tyr for Ser-79 or Asn and Ala for Asp-83 in ParC and an additional substitution in GyrA which included either Glu-85-Lys (Gly) or Ser-81-Phe (Tyr). Glu-85-Lys was found exclusively in isolates with high-level resistance. Efflux contributed primarily to low-level resistance in isolates with or without an amino acid substitution in ParC. The impact of amino acid substitutions in ParE was minimal, and no substitutions in GyrB were identified.</abstract><cop>Washington, DC</cop><pub>American Society for Microbiology</pub><pmid>11036021</pmid><doi>10.1128/AAC.44.11.3049-3054.2000</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Amino Acid Substitution Anti-Infective Agents - pharmacology Antibacterial agents Antibiotics. Antiinfectious agents. Antiparasitic agents Bacterial Proteins - genetics Bacterial Proteins - physiology Biological and medical sciences Biological Transport, Active Ciprofloxacin - pharmacology DNA Gyrase DNA Topoisomerase IV DNA Topoisomerases, Type II - genetics DNA Topoisomerases, Type II - physiology DNA-Binding Proteins - genetics DNA-Binding Proteins - physiology Drug Resistance, Microbial - genetics GyrA protein Humans Mechanisms of Resistance Medical sciences Microbial Sensitivity Tests ParC protein Pharmacology. Drug treatments Phenotype Streptococcus pneumoniae Streptococcus pneumoniae - drug effects Streptococcus pneumoniae - enzymology Streptococcus pneumoniae - genetics |
| title | Fluoroquinolone resistance in clinical isolates of Streptococcus pneumoniae : Contributions of type II topoisomerase mutations and efflux to levels of resistance |
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