title: In vitro activity of five quinolones and analysis of the quinolone resistance-determining regions of gyrA, gyrB, parC, and parE in Ureaplasma parvum and Ureaplasma urealyticum clinical isolates from perinatal patients in Japan.
abstract: Ureaplasma spp. 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 in Ureaplasma are on the rise, reports on quinolone-resistant Ureaplasma infections in Japan are limited. The purpose of this study was to determine susceptibilities to five quinolones of Ureaplasma urealyticum and Ureaplasma parvum isolated from perinatal samples in Japan and to characterize the quinolone resistance-determining regions in the gyrA, gyrB, parC, and parE genes. Out of 28 clinical Ureaplasma strains, we isolated 9 with high MICs of quinolones and found a single parC gene 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), and de novo prediction 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 of Ureaplasma spp. in Japan.
authors: Department of Developmental Medicine, Osaka Medical Center and Research Institute for Maternal and Child Health, Izumi City, Osaka, Japan.
authors: Yasuhiro
authors: Y
authors: Kawai
authors: Department of Developmental Medicine, Osaka Medical Center and Research Institute for Maternal and Child Health, Izumi City, Osaka, Japan.
authors: Yukiko
authors: Y
authors: Nakura
authors: Department of Developmental Medicine, Osaka Medical Center and Research Institute for Maternal and Child Health, Izumi City, Osaka, Japan Department of Obstetrics and Gynecology, Graduate School of Medicine, Osaka University, Suita City, Osaka, Japan.
authors: Tetsu
authors: T
authors: Wakimoto
authors: Department of Obstetrics and Gynecology, Perinatal Center, National Hospital Organization Saga National Hospital, Saga City, Saga, Japan.
authors: Makoto
authors: M
authors: Nomiyama
authors: Department of Obstetrics and Gynecology, Perinatal Center, National Hospital Organization Saga National Hospital, Saga City, Saga, Japan.
authors: Tsugumichi
authors: T
authors: Tokuda
authors: Department of Pediatrics, National Hospital Organization Saga National Hospital, Saga City, Saga, Japan.
authors: Toshimitsu
authors: T
authors: Takayanagi
authors: Department of Neonatology, Osaka Medical Center and Research Institute for Maternal and Child Health, Izumi City, Osaka, Japan.
authors: Jun
authors: J
authors: Shiraishi
authors: Department of Obstetrics and Gynecology, Aizenbashi Hospital, Osaka City, Osaka, Japan.
authors: Kenshi
authors: K
authors: Wasada
authors: Department of Neonatology, Osaka Medical Center and Research Institute for Maternal and Child Health, Izumi City, Osaka, Japan.
authors: Hiroyuki
authors: H
authors: Kitajima
authors: Fujita Clinic, Osaka City, Osaka, Japan.
authors: Tomio
authors: T
authors: Fujita
authors: Department of Pathology and Laboratory Medicine, Osaka Medical Center and Research Institute for Maternal and Child Health, Izumi City, Osaka, Japan.
authors: Masahiro
authors: M
authors: Nakayama
authors: Department of Obstetrics, Osaka Medical Center and Research Institute for Maternal and Child Health, Izumi City, Osaka, Japan.
authors: Nobuaki
authors: N
authors: Mitsuda
authors: Department of Maternal Medicine, Osaka Medical Center and Research Institute for Maternal and Child Health, Izumi City, Osaka, Japan.
authors: Isao
authors: I
authors: Nakanishi
authors: Department of Pathology and Laboratory Medicine, Osaka Medical Center and Research Institute for Maternal and Child Health, Izumi City, Osaka, Japan.
authors: Makoto
authors: M
authors: Takeuchi
authors: Department of Developmental Medicine, Osaka Medical Center and Research Institute for Maternal and Child Health, Izumi City, Osaka, Japan itaruy@mch.pref.osaka.jp.
authors: Itaru
authors: I
authors: Yanagihara
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D027081:DNA Gyrase / Q000235:genetics*; D027101:DNA Topoisomerase IV / Q000235:genetics*; D004269:DNA, Bacterial / Q000235:genetics; D024881:Drug Resistance, Bacterial / Q000187:drug effects / Q000235:genetics*; D005260:Female; D006801:Humans; D007564:Japan; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000382:microbiology; D015363:Quinolones / Q000494:pharmacology*; D017385:Sequence Homology; D014509:Ureaplasma / Q000187:drug effects* / Q000235:genetics*; D016869:Ureaplasma Infections / Q000235:genetics* / Q000382:microbiology; D016990:Ureaplasma urealyticum / Q000187:drug effects* / Q000235:genetics*
chemical_list: D004269:DNA, Bacterial; D015363:Quinolones; D027101:DNA Topoisomerase IV; D027081:DNA Gyrase
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