Alterations of the pilQ gene in Neisseria gonorrhoeae are unlikely contributors to decreased susceptibility to ceftriaxone and cefixime in clinical gonococcal strains

J Antimicrob Chemother. 2010 Dec;65(12):2543-7. doi: 10.1093/jac/dkq377. Epub 2010 Oct 12.


Objectives: Gonorrhoea remains a global public health problem and the treatment options are diminishing through the emergence of gonococci resistant to most antimicrobials. Previous in vitro studies have indicated a role for Neisseria gonorrhoeae pilQ alterations in conferring resistance to antimicrobials, including penicillin. In this study, we investigated whether pilQ polymorphisms were associated with decreased susceptibility to extended-spectrum cephalosporins (ESCs) in clinical gonococcal strains.

Methods: Full-length pilQ nucleotide and PilQ amino acid sequences from geographically and temporally diverse gonococcal clinical isolates (n = 63), including the 2008 WHO reference strains, representing a range of ceftriaxone and cefixime MICs (≤0.008-0.25 and <0.016-0.5 mg/L, respectively) and 38 N. gonorrhoeae multiantigen sequence types, were examined. Previously described alterations associated with decreased ESC susceptibility (mosaic penA, mtrR and penB alterations) were also examined.

Results: Fifteen different pilQ nucleotide sequence types and nine different PilQ amino acid sequence types were observed, with two PilQ types accounting for 53 (84%) of the isolates. Independent of other genetic resistance determinants (penA mosaic, mtrR promoter deletion and penB), only one pilQ alteration, a D526N substitution, provided a statistically significant association with ceftriaxone (P < 0.01) and cefixime (P < 0.05) MICs. However, the two isolates exhibiting D526N lacked all three previously described alterations associated with decreased ESC susceptibility, thereby providing an alternative basis for the low MICs (≤0.008 mg/L) observed for these strains. The previously described E666K (pilQ2) and F595L (pilQ1) mutations were absent in all 63 isolates.

Conclusions: pilQ polymorphisms are unlikely contributors to decreased susceptibility to ESCs in clinical gonococcal strains.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Anti-Bacterial Agents / pharmacology*
  • Cefixime / pharmacology*
  • Ceftriaxone / pharmacology*
  • Cephalosporin Resistance / genetics*
  • Fimbriae Proteins / genetics*
  • Gonorrhea / microbiology
  • Humans
  • Microbial Sensitivity Tests
  • Molecular Sequence Data
  • Mutation
  • Neisseria gonorrhoeae / drug effects*
  • Neisseria gonorrhoeae / genetics


  • Anti-Bacterial Agents
  • pilQ protein, bacteria
  • Fimbriae Proteins
  • Ceftriaxone
  • Cefixime