title: Novel penA mutations identified in Neisseria gonorrhoeae with decreased susceptibility to ceftriaxone isolated between 2000 and 2014 in Japan.
abstract: We examined four clinical strains of Neisseria gonorrhoeae (GU030113, GU110095, GU110332 and GU110362) isolated between 2000 and 2014 in Japan, exhibiting ceftriaxone MICs of 0.5 mg/L, for mutations of the genes associated with penicillin resistance.
  
  
  
  The penA, mtrR, porB1b (penB), ponA and pilQ genes of the strains were sequenced. PBP2s of the strains were aligned to the PBP2s associated with decreased susceptibility to oral cephalosporins, and PBP2s of previously reported strains with decreased susceptibility to ceftriaxone.
  
  
  
  GU030113 had PBP2 pattern X with an additional substitution of A502T. GU110095 had PBP2 pattern XXVII. GU110332 had PBP2 pattern XXXIV with an additional substitution of P552S. GU110362 had PBP2 composed of pattern X (amino acid positions 1-291) and pattern V (amino acid positions 292-576). GU030113, GU110095 and GU110332 had deletion of A in the mtrR promoter, G120K and A121D or A121N in PorB1b and L421P in PBP1. GU110362 had A40D in the repressor of MtrR and L421P in PBP1. The strains did not have mutations of pilQ1 and pilQ2.
  
  
  
  Addition of A502T to PBP2 pattern X in GU030113 and of P552S to PBP2 pattern XXXIV in GU110332 would possibly contribute to decreased susceptibility to ceftriaxone. In GU110095 and GU110362, it was suggested that, in addition to their altered PBP2s, the enhanced efflux pump, reduced permeability in the outer membrane, another altered target of β-lactams and/or other mechanisms not identified in the present study might contribute to decreased susceptibility.
authors.affiliation: Department of Urology, Graduate School of Medicine, Gifu University, Gifu, Japan.
authors.forename: Kensaku
authors.initials: K
authors.lastname: Seike
authors.affiliation: Department of Urology, Graduate School of Medicine, Gifu University, Gifu, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Yasuda
authors.affiliation: Department of Urology, Graduate School of Medicine, Gifu University, Gifu, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Hatazaki
authors.affiliation: Department of Urology, Graduate School of Medicine, Gifu University, Gifu, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Mizutani
authors.affiliation: Department of Urology, Japanese Red Cross Takayama Hospital, Takayama, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Yuhara
authors.affiliation: Department of Urology, Ibi Kosei Hospital, Ibi, Japan.
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Ito
authors.affiliation: Department of Urology, Ogaki Municipal Hospital, Ogaki, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Fujimoto
authors.affiliation: iClinic, Sendai, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Ito
authors.affiliation: Department of Urology, Graduate School of Medicine, Gifu University, Gifu, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Tsuchiya
authors.affiliation: Department of Urology, Graduate School of Medicine, Gifu University, Gifu, Japan.
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Yokoi
authors.affiliation: Department of Urology, Graduate School of Medicine, Gifu University, Gifu, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nakano
authors.affiliation: Department of Urology, Graduate School of Medicine, Gifu University, Gifu, Japan deguchit@gifu-u.ac.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Deguchi
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000378:metabolism*; D002443:Ceftriaxone / Q000494:pharmacology*; D004252:DNA Mutational Analysis; D024881:Drug Resistance, Bacterial; D005260:Female; D006069:Gonorrhea / Q000382:microbiology; D006801:Humans; D007564:Japan; D008297:Male; D008826:Microbial Sensitivity Tests; D009154:Mutation; D009344:Neisseria gonorrhoeae / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002443:Ceftriaxone