Fluoroquinolone resistance in clinical isolates of Streptococcus pneumoniae : Contributions of type II topoisomerase mutations and efflux to levels of resistance

• Published in: Antimicrobial agents and chemotherapy Vol. 44; no. 11; pp. 3049 - 3054
• Main Authors: BAST, Darrin J, LOW, Donald E, DUNCAN, Carla L, KILBURN, Laurie, MANDELL, Lionel A, DAVIDSON, Ross J, DE AZAVEDO, Joyce C. S
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for Microbiology 01-11-2000
• 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; DNA topoisomerase (ATP-hydrolysing); Enzyme; Norfloxacin; Ofloxacin; In vitro; Streptococcus pneumoniae; Resistance; Streptococcaceae; Fluoroquinolone derivatives; Isomerases; Substitution; Aminoacid; Bacteria; Micrococcales; Mutation; Antibacterial agent; Ciprofloxacin; Quinolone derivatives
• ISSN: 0066-4804; 1098-6596
• DOI: 10.1128/AAC.44.11.3049-3054.2000

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.