부산대학교 도서관

Background & Objectives: Moraxella catarrhalis is a gram-negative aerobic diplococcus that causes respiratory infections. Because the mechanism of M. catarrhalis resistance to fluoroquinolone is unclear, fluoroquinolone resistant strains were selected in vitro to evaluate the mechanism of resistance. Methods: Strains with reduced fluoroquinolone susceptibility were obtained by stepwise selection in levofloxacin. Antimicrobial susceptibility to levofloxacin and ciprofloxacin were assessed by broth microdilution and disk diffusion methods. PCR and sequencing of the gyr and par genes were performed. Overexpression of the efflux system was investigated using two efflux pump inhibitors, phenylalanine-arginine β-naphthylamide (PAβN) and carbonyl cyanide m-chlorophenylhydrazone (CCCP). Results: In total, 14 variants with elevated fluoroquinolone minimum inhibitory concentration (MIC; levofloxacin MIC, 0.25-16 mg/L) were obtained following the selection. The inhibitory diameter using levofloxacin disks (5 μg) was <20 mm for all fluoroquinolone-resistant variants obtained in this study. Three and two types of substitutions or duplications were observed in GyrA (D84Y, T594dup, and A722dup) and GyrB (E479K and D439N), respectively. A duplication was observed in ParC (T568dup), and a substitution was found in ParE (Q395R). Transformation experiments revealed that the Gyr substitutions were more critical than those in Par for fluoroquinolone resistance in M. catarrhalis and other gram-negative bacteria. However, the two efflux pump inhibitors did not alter the MICs. Conclusion: This study revealed six novel mutations in gyrA, gyrB, and parE genes that were involved in M. catarrhalis resistance to fluoroquinolones. This is the first study to describe a detailed mechanism of fluoroquinolone resistance in M. catarrhalis.