Background Antimicrobial resistance to third generation cephalosporins, penicillin and tetracycline in Neisseria gonorrhoeae isolates can be associated with particular strain types (STs) as well as specific mutation patterns in penA, mtrR or porB. With a view to developing molecular diagnostics for antimicrobial susceptibility, we investigated whether antibiotic resistant and susceptible N. gonorrhoeae isolates from Saskatchewan Canada were associated with specific STs and combined mutation patterns in penA, mtrR or porB.
Methods DNA sequences of penA, mtrR and porB for 146 N. gonorrhoeae isolates were compared to “wild type” penA (GenBank#M32091), mtrR (GenBank#Z25796) and porB (GenBank#M21289) sequences. Mutation pattern numbers for penA were assigned as described by others. STs were ascertained by NG-MAST. Isolates were selected based on antimicrobial susceptibility phenotypes to 7 antibiotics.
Results Strains were classified into 51 NG-MAST STs; 6 STs (86/146; 59%) comprised ≥ 5 isolates, 10 STs included 2–4 isolates, and 35 STs contained 1 isolate. Isolates with ST 25 (33/36, 92%) were associated (P < 0.0001) with penA/mtrR/porB pattern I/WT/WT and with antibiotic susceptibility. ST 3654 was associated (P < 0.0001) with penA/mtrR/porB pattern IX/G45D/G120K,A121D (n = 13/17) and CMRNG (n = 7) or CMTR (n = 6) isolates. Isolates with chromosomal resistance to tetracycline were significantly associated (P < 0.0001) with several STs and penA/mtrR/porB patterns including: ST 3655 (XXII/A-,G45D/G120N,A121N - n = 8/12), ST 921 (pattern IX/G45D/G120D,A121N - n = 6/9), ST 508 (XXII/G45D/G120D,A121N - n = /6), and ST 3656 (pattern XXII/A-,G45D/G120D,A121N - n = 5/6). 24 isolates had higher cefixime MICs (0.03–0.06 mg/L) and included 17 STs with penA pattern IX (n = 17) and mtrR G45D (n = 16) and porB G120K,A121D (n = 12) mutations. Seven of these isolates were associated (P < 0.0001) with ST 3654 (pattern IX/G45D/G120K,A121D).
Conclusions We identified significant associations between particular mutation pattern combinations in penA, mtrR and porB and specific STs. This indicates that certain combined mutation patterns may be predictive of antimicrobial susceptibility and useful for molecular diagnosis.
- antibiotic resistance
- N. gonorrhoeae