title: Azithromycin resistance and its mechanism in Neisseria gonorrhoeae strains in Hyogo, Japan.
abstract: Therapeutic options are limited for Neisseria gonorrhoeae infection, especially for oral drugs. The purpose of this study was to investigate the susceptibility of N. gonorrhoeae to oral azithromycin (AZM) and the correlation between AZM resistance-related gene mutations and MIC. We examined the AZM MICs of clinical strains of N. gonorrhoeae, sequenced the peptidyltransferase loop in domain V of 23S rRNA, and investigated the statistical correlation between AZM MIC and the presence and number of the mutations. Among 59 N. gonorrhoeae strains, our statistical data showed that a deletion mutation was seen significantly more often in the higher-MIC group (0.5 μg/ml or higher) (35/37; 94.6%) than in the lower-MIC group (0.25 μg/ml or less) (4/22; 18.2%) (P < 0.0001). However, a mutation of codon 40 (Ala → Asp) in the mtrR gene (helix-turn-helix) was seen significantly more often in the lower-MIC group (12/22; 54.5%) (P < 0.0001). In N. gonorrhoeae multiantigen sequence typing (NG-MAST) analyses, ST4777 was representative of the lower-MIC group and ST1407, ST6798, and ST6800 were representative of the higher-MIC group. NG-MAST type 1407 was detected as the most prevalent type in AZM-resistant or -intermediate strains, as previously described. In conclusion, a deletion mutation in the mtrR promoter region may be a significant indicator for higher MIC (0.5 μg/ml or higher). ST4777 was often seen in the lower-MIC group, and ST1407, ST6798, and ST6800 were characteristic of the higher-MIC group. Further research with a greater number of strains would help elucidate the mechanism of AZM resistance in N. gonorrhoeae infection.
authors.affiliation: Division of Urology, Department of Organ Therapeutics, Faculty of Medicine, Kobe University Graduate School of Medicine, Kobe, Japan Department of Infection Control and Prevention, Kobe University Hospital, Kobe, Japan yutoshunta@hotmail.co.jp.
authors.forename: Katsumi
authors.initials: K
authors.lastname: Shigemura
authors.affiliation: Department of Infection Control and Prevention, Kobe University Hospital, Kobe, Japan Division of Infectious Diseases, Department of International Health, Kobe University Graduate School of Health Science, Kobe, Japan.
authors.forename: Kayo
authors.initials: K
authors.lastname: Osawa
authors.affiliation: Division of Infectious Diseases, Department of International Health, Kobe University Graduate School of Health Science, Kobe, Japan Department of Medical Technology, Kobe Tokiwa University, Kobe, Japan.
authors.forename: Makiko
authors.initials: M
authors.lastname: Miura
authors.affiliation: Division of Urology, Department of Organ Therapeutics, Faculty of Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Kazushi
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Division of Urology, Department of Organ Therapeutics, Faculty of Medicine, Kobe University Graduate School of Medicine, Kobe, Japan Department of Infection Control and Prevention, Kobe University Hospital, Kobe, Japan.
authors.forename: Soichi
authors.initials: S
authors.lastname: Arakawa
authors.affiliation: Division of Urology, Department of Organ Therapeutics, Faculty of Medicine, Kobe University Graduate School of Medicine, Kobe, Japan Division of Infectious Diseases, Department of International Health, Kobe University Graduate School of Health Science, Kobe, Japan Center for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Toshiro
authors.initials: T
authors.lastname: Shirakawa
authors.affiliation: Division of Urology, Department of Organ Therapeutics, Faculty of Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Fujisawa
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017963:Azithromycin / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial / Q000235:genetics; D007564:Japan; D008826:Microbial Sensitivity Tests; D009344:Neisseria gonorrhoeae / Q000187:drug effects*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D017963:Azithromycin