title: Genetic diversity of blaTEM alleles, antimicrobial susceptibility and molecular epidemiological characteristics of penicillinase-producing Neisseria gonorrhoeae from England and Wales.
abstract: OBJECTIVE
  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.
authors: Sexually Transmitted Bacteria Reference Unit, Public Health England, London, UK michelle.cole@phe.gov.uk.
authors: Michelle J
authors: MJ
authors: Cole
authors: WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Microbiology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
authors: Magnus
authors: M
authors: Unemo
authors: Sexually Transmitted Bacteria Reference Unit, Public Health England, London, UK.
authors: Vlad
authors: V
authors: Grigorjev
authors: National Mycobacterium Reference Laboratory, Public Health England, London, UK.
authors: Nerteley
authors: N
authors: Quaye
authors: Antimicrobial Resistance and Healthcare Associated Infections Reference Unit, Public Health England, London, UK.
authors: Neil
authors: N
authors: Woodford
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004739:England / Q000453:epidemiology; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006069:Gonorrhea / Q000453:epidemiology*; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D017720:Molecular Epidemiology; D009344:Neisseria gonorrhoeae / Q000145:classification* / Q000187:drug effects* / Q000201:enzymology / Q000302:isolation & purification; D010405:Penicillinase / Q000032:analysis* / Q000235:genetics*; D010957:Plasmids / Q000032:analysis; D014852:Wales / Q000453:epidemiology; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D010405:Penicillinase