In VitroActivity of Five Quinolones and Analysis of the Quinolone Resistance-Determining Regions ofgyrA,gyrB,parC, andparEin Ureaplasma parvum and Ureaplasma urealyticum Clinical Isolates from Perinatal Patients in Japan

Abstract

ABSTRACTUreaplasmaspp. cause several disorders, such as nongonococcal urethritis, miscarriage, and preterm delivery with lung infections in neonates, characterized by pathological chorioamnionitis in the placenta. Although reports on antibiotic resistance inUreaplasmaare on the rise, reports on quinolone-resistantUreaplasmainfections in Japan are limited. The purpose of this study was to determine susceptibilities to five quinolones ofUreaplasma urealyticumandUreaplasma parvumisolated from perinatal samples in Japan and to characterize the quinolone resistance-determining regions in thegyrA,gyrB,parC, andparEgenes. Out of 28 clinicalUreaplasmastrains, we isolated 9 with high MICs of quinolones and found a singleparCgene mutation, resulting in the change S83L. Among 158 samples, the ParC S83L mutation was found in 37 samples (23.4%), including 1 sample harboring a ParC S83L–GyrB P462S double mutant. Novel mutations of ureaplasmal ParC (S83W and S84P) were independently found in one of the samples. Homology modeling of the ParC S83W mutant suggested steric hindrance of the quinolone-binding pocket (QBP), andde novoprediction of peptide structures revealed that the ParC S84P may break/kink the formation of the α4 helix in the QBP. Further investigations are required to unravel the extent and mechanism of antibiotic resistance ofUreaplasmaspp. in Japan.