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- Title
Alterations of the pilQ gene in Neisseria gonorrhoeae are unlikely contributors to decreased susceptibility to ceftriaxone and cefixime in clinical gonococcal strains.
- Authors
Whiley, David M.; Jacobsson, Susanne; Tapsall, John W.; Nissen, Michael D.; Sloots, Theo P.; Unemo, Magnus
- Abstract
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.
- Subjects
NEISSERIA gonorrhoeae; ANTI-infective agents; ANTIBIOTICS; PENICILLIN; CEPHALOSPORINS; ANTIBACTERIAL agents
- Publication
Journal of Antimicrobial Chemotherapy (JAC), 2010, Vol 65, Issue 12, p2543
- ISSN
0305-7453
- Publication type
Article
- DOI
10.1093/jac/dkq377