Abstract : OBJECTIVES Reduced susceptibility to extended-spectrum cephalosporins in Neisseria gonorrhoeae has
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Abstract : OBJECTIVES Reduced susceptibility to extended-spectrum cephalosporins in Neisseria gonorrhoeae has to date been associated with three alterations a mosaic penA allele encoding the penicillin-binding protein 2 (PBP2) A-del-mtrR an adenine deletion in the mtrR promoter and penB comprising mutated alleles of PorBIb. In this study we examined an association between reduced susceptibility to ceftriaxone and additional mutations in gonococcal PBP2.|METHODS N. gonorrhoeae isolates (n = 76) exhibiting reduced susceptibility to ceftriaxone but lacking the mosaic penA sequence were investigated for A-del-mtrR and penB as well as substitutions at PBP2 501 542 and 551 using a previously described real-time PCR approach. To further investigate PBP2 542 and 551 substitutions we reanalysed penA sequence data from a previous study of 98 gonococci exhibiting a range of ceftriaxone MICs.|RESULTS Of 76 N. gonorrhoeae isolates exhibiting reduced susceptibility to ceftriaxone and lacking the mosaic penA sequence a 501 (A501V or A501T) substitution was present in 9/76 a 542 substitution in 39/76 and a 551 substitution in 26/76 isolates. Reanalysis of 98 gonococcal isolates from a previous study showed that substitutions at PBP2 542 (G542S) and 551 (P551S or P551L) were significantly associated with raised MICs to ceftriaxone (P = 0.0186 and 0.001 respectively) and penicillin (P = 0.0231 and 0.0007 respectively).|CONCLUSIONS: Our findings provide strong evidence for the involvement of PBP2 G542S and P551S/P551L in reduced susceptibility to ceftriaxone and to penicillin. Further studies are needed to investigate the precise and relative roles played by these mutations.|
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