title: Spread of a chromosomal cefixime-resistant penA gene among different Neisseria gonorrhoeae lineages.
abstract: In Neisseria gonorrhoeae, the mosaic type of penA, which encodes penicillin-binding protein 2 (PBP 2), is associated with reduced susceptibility to oral cephalosporins. To investigate the relatedness of N. gonorrhoeae clinical isolates with reduced susceptibility, we sequenced the penA genes of 32 isolates. Five different amino acid sequence types of PBP 2 were identified, but all seemed to be derivatives of pattern X of PBP 2 (PBP 2-X). However, multilocus sequence typing of the isolates showed that the isolates belonged to six different sequence types. As PBP 2-X was identified in three different sequence types, horizontal transfer of the penA allele encoding PBP2-X was suggested. We demonstrated that the penA gene could be transferred from an isolate with reduced susceptibility to a sensitive isolate by natural transformation. Comparison of the sequence of the penA-flanking regions of 12 transformants with those of the donor and the recipient suggested that at least a 4-kb DNA segment, including the penA gene, was transferred. During horizontal transfer, some of the penA alleles also acquired variations due to point mutations and genetic exchange within the allele. Our results provide evidence that the capacity for natural transformation in N. gonorrhoeae plays a role in the spread of chromosomal antibiotic resistance genes and the generation of diversity in such genes.
authors.affiliation: Department of Bacteriology, National Institute of Infectious Diseases, 1-23-1, Toyama, Shinjuku, Tokyo 162-8640, Japan. ohnishi7@nih.go.jp
authors.forename: Makoto
authors.initials: M
authors.lastname: Ohnishi
authors.forename: Yuko
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Emi
authors.initials: E
authors.lastname: Ono
authors.forename: Chieko
authors.initials: C
authors.lastname: Takahashi
authors.forename: Hitomi
authors.initials: H
authors.lastname: Oya
authors.forename: Toshiro
authors.initials: T
authors.lastname: Kuroki
authors.forename: Ken
authors.initials: K
authors.lastname: Shimuta
authors.forename: Norio
authors.initials: N
authors.lastname: Okazaki
authors.forename: Shu-ichi
authors.initials: S
authors.lastname: Nakayama
authors.forename: Haruo
authors.initials: H
authors.lastname: Watanabe
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001483:Base Sequence; D020682:Cefixime / Q000494:pharmacology*; D018550:Cephalosporin Resistance / Q000235:genetics*; D002876:Chromosomes, Bacterial / Q000235:genetics; D006069:Gonorrhea / Q000382:microbiology / Q000635:transmission; D006801:Humans; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009344:Neisseria gonorrhoeae / Q000145:classification / Q000187:drug effects / Q000235:genetics; D046915:Penicillin-Binding Proteins / Q000737:chemistry / Q000235:genetics*; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
chemical_list: D000900:Anti-Bacterial Agents; D046915:Penicillin-Binding Proteins; D020682:Cefixime