Analysis of Amino Acid Sequences of Penicillin-Binding Protein 2 in Clinical Isolates of Neisseria Gonorrhoeae With Reduced Susceptibility to Cefixime and Ceftriaxone

J Infect Chemother. 2008 Jun;14(3):195-203. doi: 10.1007/s10156-008-0610-7. Epub 2008 Jun 24.

Abstract

Neisseria gonorrhoeae strains with reduced susceptibility to cefixime and ceftriaxone, with minimum inhibitory concentrations (MICs) of cefixime of 0.125-0.25 microg/ml and ceftriaxone of 0.031-0.125 microg/ml, were isolated from male urethritis patients in Tokyo, Japan, in 2006. The amino acid sequences of PenA, penicillin-binding protein 2, in these strains were of two types: PenA mosaic and nonmosaic strains. In the PenA mosaic strain, some regions in the transpeptidase-encoding domain in PenA were similar to those of Neisseria perflava/sicca, Neisseria cinerea, Neisseria flavescens, Neisseria polysaccharea, and Neisseria meningitidis. In the PenA nonmosaic strain, there was a mutation of Ala-501 to Val in PenA. In addition, we performed homology modeling of PenA wild-type and mosaic strains and compared them. The results of the modeling studies suggested that reduced susceptibility to cephems such as cefixime and ceftriaxone is due to a conformational alteration of the beta-lactam-binding pocket. These results also indicated that the mosaic structures and the above point mutation in PenA make a major contribution to the reduced susceptibility to cephem antibiotics.

MeSH terms

  • Amino Acid Sequence / physiology
  • Anti-Bacterial Agents / pharmacology*
  • Cefixime / pharmacology*
  • Ceftriaxone / pharmacology*
  • Drug Resistance, Multiple, Bacterial
  • Humans
  • Male
  • Microbial Sensitivity Tests
  • Mutation
  • Neisseria gonorrhoeae / drug effects*
  • Penicillin-Binding Proteins / chemistry*
  • Penicillin-Binding Proteins / drug effects
  • Penicillin-Binding Proteins / genetics
  • Sequence Analysis, Protein
  • Urethritis / microbiology
  • beta-Lactamases / metabolism

Substances

  • Anti-Bacterial Agents
  • Penicillin-Binding Proteins
  • Ceftriaxone
  • Cefixime
  • beta-Lactamases