Frequency of 1st- and 2nd-step topoisomerase mutations in Streptococcus pneumoniae following levofloxacin and moxifloxacin exposure.
Seven Streptococcus pneumoniae isolates were exposed to inhibitory concentrations of levofloxacin and moxifloxacin in antibiotic-containing agar dilution plates. Colony counts were used to calculate the frequency of mutation. DNA was sequenced to detect mutations in the quinolone resistance-determining regions of the gyrA, gyrB, parC, and parE genes. The wild-type S. pneumoniae isolate developed a parC mutation after exposure to levofloxacin more frequently than it developed a gyrA mutation after exposure to moxifloxacin. The 1st-step gyrA mutant developed a 2nd-step gyrA-parC mutation more frequently after exposure to levofloxacin. Conversely, the transformation from a 1st-step parC mutant to a 2nd-step parC-gyrA mutant occurred more frequently following exposure to moxifloxacin. Our data suggest that the occurrence of a 2nd mutation will be contingent on the location of the 1st mutation and the preferential binding site of the fluoroquinolone that drives the transformation from 1st- to 2nd-step mutant.
Hovde
Laurie B
LB
Department of Experimental and Clinical Pharmacology, Antibiotic Pharmacodynamic Research Institute, The University of Minnesota College of Pharmacy, Minneapolis, MN 55455, USA.
Simonson
Dana A
DA
Rotschafer
John C
JC
D019943:Amino Acid Substitution / Q000235:genetics; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001372:Aza Compounds / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics*; D015169:Colony Count, Microbial; D026942:DNA Topoisomerases / Q000235:genetics*; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D024841:Fluoroquinolones; D064704:Levofloxacin; D000077266:Moxifloxacin; D020125:Mutation, Missense; D015242:Ofloxacin / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D011804:Quinolines / Q000494:pharmacology*; D017422:Sequence Analysis, DNA; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000235:genetics
D000900:Anti-Bacterial Agents; D001372:Aza Compounds; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D024841:Fluoroquinolones; D011804:Quinolines; D064704:Levofloxacin; D015242:Ofloxacin; D026942:DNA Topoisomerases; D000077266:Moxifloxacin