Susceptibility and resistance genes to fluoroquinolones in methicillin-resistant Staphylococcus aureus isolated in 2002.
The activity of six fluoroquinolones (FQs) was determined against 100 methicillin-resistant Staphylococcus aureus (MRSA) isolated in 2002 along with mutations in the grlA and gyrA genes and in the norA promoter of these isolates. Of the isolates tested, 97% had mutations in grlA and gyrA. A single mutation in grlA and gyrA resulted in a decrease of susceptibility to old generation FQs (norfloxacin, enoxacin, ciprofloxacin, fleroxacin, sparfloxacin and levofloxacin) but not to new generation FQs (gatifloxacin and moxifloxacin). Double mutations of both grlA and gyrA resulted in high-level resistance to all FQs tested. All norA mutants (15%) contained double mutations in grlA and gyrA and showed no decrease of MIC in the presence of reserpine, which is known to inhibit the drug-efflux pump. Our results showed that double mutations in grlA and gyrA were necessary for the expression of high-level resistance to new generation FQs. As different FQ-resistant mutants occur in the same PFGE type, FQ-resistant MRSA may well develop individually.
Noguchi
Norihisa
N
Department of Microbiology, School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan. noguchin@ps.toyaku.ac.jp
Okihara
Takeshi
T
Namiki
Yuta
Y
Kumaki
Yuichi
Y
Yamanaka
Yoshihiro
Y
Koyama
Masaharu
M
Wakasugi
Kazunori
K
Sasatsu
Masanori
M
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics; D001483:Base Sequence; D027081:DNA Gyrase / Q000235:genetics; D024841:Fluoroquinolones / Q000494:pharmacology*; D006801:Humans; D016106:Methicillin Resistance / Q000187:drug effects / Q000235:genetics; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics; D009154:Mutation; D011401:Promoter Regions, Genetic; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000517:prevention & control; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D027081:DNA Gyrase; D024841:Fluoroquinolones; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C075040:NorA protein, Staphylococcus