title: Diversity of penA alterations and subtypes in Neisseria gonorrhoeae strains from Sydney, Australia, that are less susceptible to ceftriaxone.
abstract: Increasing numbers of Neisseria gonorrhoeae strains with decreased susceptibilities to ceftriaxone and other oral cephalosporins widely used for the treatment of gonorrhea have been isolated in Sydney, Australia, over several years. In this study, we examined the complete penicillin-binding protein 2 (PBP 2) amino acid sequences of 109 gonococci, selected on the basis of their diverse temporal and geographic origins and because they exhibited a range of ceftriaxone MICs: < OR =0.03 microg/ml (n = 59), 0.06 microg/ml (n = 43), and 0.125 microg/ml (n = 7). Auxotyping, serotyping, and genotyping by N. gonorrhoeae multiantigen sequence typing sequence-based analysis was also performed. In total, 20 different amino acid sequence patterns were identified, indicating considerable variation in the PBP 2 sequences in this study sample. Only some of the N. gonorrhoeae isolates with significantly higher ceftriaxone MICs contained a mosaic PBP 2 pattern, while more isolates exhibited a nonmosaic PBP 2 pattern containing an A501V substitution. Although particular N. gonorrhoeae genotypes in our sample were shown to be less susceptible to ceftriaxone, the reduced susceptibility to ceftriaxone was not specific to any particular genotype and was observed in a broad range of auxotypes, serotypes, and genotypes. Overall, the results of our study show that N. gonorrhoeae strains exhibiting reduced sensitivity to ceftriaxone are not of a particular subtype and that a number of different mutations in PBP 2 may contribute to this phenomenon.
authors.affiliation: Queensland Paediatric Infectious Diseases Laboratory, Sir Albert Sakzewski Virus Research Centre, Royal Children's Hospital and Health Service District, Brisbane, Queensland, Australia.
authors.forename: David M
authors.initials: DM
authors.lastname: Whiley
authors.forename: E Athena
authors.initials: EA
authors.lastname: Limnios
authors.forename: Sanghamitra
authors.initials: S
authors.lastname: Ray
authors.forename: Theo P
authors.initials: TP
authors.lastname: Sloots
authors.forename: John W
authors.initials: JW
authors.lastname: Tapsall
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001315:Australia / Q000453:epidemiology; D002443:Ceftriaxone / Q000494:pharmacology*; D005838:Genotype; D006069:Gonorrhea / Q000382:microbiology; D006801:Humans; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics / Q000502:physiology; D009344:Neisseria gonorrhoeae / Q000187:drug effects* / Q000235:genetics*; D046915:Penicillin-Binding Proteins / Q000235:genetics*; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000900:Anti-Bacterial Agents; D046915:Penicillin-Binding Proteins; D002443:Ceftriaxone