Background Third-generation cephalosporins (eg, ceftriaxone, Cro) are the antimicrobials of choice for the treatment of gonorrhoea. The molecular mechanisms causing reduced susceptibility to these antibiotics in Neisseria gonorrhoeae (Ng) isolates differ between isolates from different geographic regions. The objective of this research was to characterise mutations in penA, mtrR, porB and ponA associated with Cro reduced susceptibility (CroRed) in Ng isolates from Saskatchewan (SK), Canada.
Methods A total of 320 of Ng isolates (2003 to 2008) from SK were tested for their antimicrobial susceptibility to Cro using the CLSI agar dilution method. 7% of the isolates (n=23) had Cro MICs of 0.03–0.06 mg/l and were defined as having CroRed phenotypes and 93% of the isolates (n=297) had MICs of <0.03 mg/l which were classified as susceptible (CroS). All CroRed isolates were analysed for mutations in penA (PBP2), mtrR (MtrR), porB (PorB) and ponA (PBP1). 123 (42%) CroS isolates were randomly selected as coselected
Results In total, nine mutation patterns were observed in penA. Patterns I (31.7%), IX (29.2%) and XXII (26%) were most common in the 123 CroS isolates; while patterns IX (60.8%, p<0.05) and XXII (21.5%, p>0.05) were predominant in the 23 CroRed isolates. The mosaic penA pattern X was observed in only one isolate (Cro MIC=0.06 mg/l). Seven mutation patterns were noted in mtrR. Among the CroS isolates, 35.8% had a single mutation (G45D or A39T) in the DNA binding domain (DBD) and 17.8% of the isolates carried an A" nucleotide deletion (A−) in the mtr promoter coupled with a G45D mutation. Among the CroRed isolates, 65.2% carried G45D or A39T single mutations, significantly higher than that of CroS isolates (p<0.05). The mutation of A−/H105Y was observed in 21.7% of CroRed isolates as compared to 4% of CroS isolates (p<0.05). Five mutation patterns at residues G120 and A121 of PorB were observed in the CroRed isolates including double (47.8% vs 13% CroS isolates, p<0.05) or single (21.7% vs 26% CroS isolates, p>0.05) mutations. L421P in PBP1 was detected in 87% CroRed and 13% CroS isolates, respectively (p<0.05).
Conclusions Mosaic penA pattern X was only observed in one CroRed isolate. The mutations associated with CroRed phenotypes include pattern IX of PBP2, mutations in DBD and a double mutation of A−/H105Y in mtrR, double mutations in PorB (positions G120 and A121) and L421P of PBP1.
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