| Abstrakt: |
ABSTRACTMutations associated with fluoroquinolone resistance in clinical isolates of Proteus mirabiliswere determined by genetic analysis of the quinolone resistance-determining region (QRDR) of gyrA, gyrB, parC, and parE. This study included the P. mirabilistype strain ATCC 29906 and 29 clinical isolates with reduced susceptibility (MIC, 0.5 to 2 μg/ml) or resistance (MIC, ≥4 μg/ml) to ciprofloxacin. Susceptibility profiles for ciprofloxacin, clinafloxacin, gatifloxacin, gemifloxacin, levofloxacin, moxifloxacin, and trovafloxacin were correlated with amino acid changes in the QRDRs. Decreased susceptibility and resistance were associated with double mutations involving both gyrA(S83R or -I) and parC(S80R or -I). Among these double mutants, MICs of ciprofloxacin varied from 1 to 16 μg/ml, indicating that additional factors, such as drug efflux or porin changes, also contribute to the level of resistance. For ParE, a single conservative change of V364I was detected in seven strains. An unexpected result was the association of gyrBmutations with high-level resistance to fluoroquinolones in 12 of 20 ciprofloxacin-resistant isolates. Changes in GyrB included S464Y (six isolates), S464F (three isolates), and E466D (two isolates). A three-nucleotide insertion, resulting in an additional lysine residue between K455 and A456, was detected in gyrBof one strain. Unlike any other bacterial species analyzed to date, mutation of gyrBappears to be a frequent event in the acquisition of fluoroquinolone resistance among clinical isolates of P. mirabilis. |
