Genetic Diversity of blaTEM Alleles, Antimicrobial Susceptibility and Molecular Epidemiological Characteristics of Penicillinase-Producing Neisseria Gonorrhoeae From England and Wales

J Antimicrob Chemother. 2015 Dec;70(12):3238-43. doi: 10.1093/jac/dkv260. Epub 2015 Aug 27.

Abstract

Objectives: The objective of this study was to investigate the genetic diversity of blaTEM alleles, antimicrobial susceptibility and molecular epidemiological characteristics of penicillinase-producing Neisseria gonorrhoeae (PPNG) isolates collected in 2012 from England and Wales.

Methods: PPNG isolates were from the 2012 Gonococcal Resistance to Antimicrobial Surveillance Programme (GRASP). Their susceptibility to seven antimicrobials was determined using agar dilution methodology. β-Lactamase production was detected using a nitrocefin test. β-Lactamase plasmid types were determined and blaTEM genes were sequenced. Isolates were also typed by N. gonorrhoeae multi-antigen sequence typing (NG-MAST).

Results: Seventy-three PPNG isolates were identified in the 2012 GRASP collection (4.6%, 73/1603). Three different blaTEM alleles were identified, encoding three TEM amino acid sequences: TEM-1 (53%), TEM-1 with a P14S substitution (19%) and TEM-135 (27%). The blaTEM-135 allele was present in nine different NG-MAST types and was found mostly on Asian (60%) and Toronto/Rio (35%) plasmids. By contrast, most TEM-1-encoding plasmids were African (98%). All the TEM-135 isolates displayed high-level ciprofloxacin and tetracycline resistance.

Conclusions: The high proportion of blaTEM-135 alleles (27%) demonstrates that this variant is circulating within several gonococcal lineages. Only a single specific mutation near the β-lactamase active site could result in TEM-135 evolving into an ESBL. This is concerning particularly because the TEM-135 isolates were associated with high-level ciprofloxacin and tetracycline resistance. It is encouraging that no further TEM alleles were detected in this gonococcal population; however, vigilance is vital as an ESBL in N. gonorrhoeae would render the last remaining option for monotherapy, ceftriaxone, useless.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Alleles
  • Anti-Bacterial Agents / pharmacology*
  • England / epidemiology
  • Female
  • Genetic Variation*
  • Genotype
  • Gonorrhea / epidemiology*
  • Humans
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Molecular Epidemiology
  • Neisseria gonorrhoeae / classification*
  • Neisseria gonorrhoeae / drug effects*
  • Neisseria gonorrhoeae / enzymology
  • Neisseria gonorrhoeae / isolation & purification
  • Penicillinase / analysis*
  • Penicillinase / genetics*
  • Plasmids / analysis
  • Wales / epidemiology
  • Young Adult

Substances

  • Anti-Bacterial Agents
  • Penicillinase