Open AccessSpread of a Chromosomal Cefixime-Resistant penA Gene among Different Neisseria gonorrhoeae Lineages
Author(s) -
Makoto Ohnishi,
Yuko Watanabe,
Emi Ono,
Chieko Takahashi,
Hitomi Oya,
Toshiro Kuroki,
Ken Shimuta,
Norio Okazaki,
Shuichi Nakayama,
Haruo Watanabe
Publication year - 2010
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.01010-09
Subject(s) - neisseria gonorrhoeae , biology , genetics , multilocus sequence typing , gene , horizontal gene transfer , transformation (genetics) , allele , point mutation , cefixime , mutation , genotype , cephalosporin , phylogenetic tree , antibiotics
InNeisse ria gonorrhoeae , the mosaic type ofpenA , which encodes penicillin-binding protein 2 (PBP 2), is associated with reduced susceptibility to oral cephalosporins. To investigate the relatedness ofN. gonorrhoeae clinical isolates with reduced susceptibility, we sequenced thepenA 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 thepenA allele encoding PBP2-X was suggested. We demonstrated that thepenA gene could be transferred from an isolate with reduced susceptibility to a sensitive isolate by natural transformation. Comparison of the sequence of thepenA -flanking regions of 12 transformants with those of the donor and the recipient suggested that at least a 4-kb DNA segment, including thepenA gene, was transferred. During horizontal transfer, some of thepenA alleles also acquired variations due to point mutations and genetic exchange within the allele. Our results provide evidence that the capacity for natural transformation inN. gonorrhoeae plays a role in the spread of chromosomal antibiotic resistance genes and the generation of diversity in such genes.