Queensland Paediatric Infectious Diseases Laboratory, Queensland Children's Medical Research Institute, Children's Health Service District, Queensland, Australia.
J Antimicrob Chemother. 2010 Aug;65(8):1615-8. doi: 10.1093/jac/dkq187. Epub 2010 May 28.
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.
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.
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).
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.
淋病奈瑟菌对扩展谱头孢菌素的敏感性降低，迄今为止，与三种改变有关：编码青霉素结合蛋白 2（PBP2）的马赛克 penA 等位基因；mtrR 启动子中的腺嘌呤缺失 A-del-mtrR；以及包含突变的 PorBIb 等位基因的 penB。在这项研究中，我们研究了淋病奈瑟菌 PBP2 中除了降低对头孢曲松的敏感性以外的其他突变与敏感性之间的关系。
研究了 76 株对头孢曲松表现出耐药性但缺乏马赛克 penA 序列的淋病奈瑟菌分离株，这些分离株是否存在 A-del-mtrR 和 penB 以及 PBP2 501、542 和 551 处的取代，使用了之前描述的实时 PCR 方法。为了进一步研究 PBP2 542 和 551 取代，我们重新分析了之前对 98 株具有不同头孢曲松 MIC 值的淋病奈瑟菌进行的研究中的 penA 序列数据。
在 76 株对头孢曲松表现出耐药性且缺乏马赛克 penA 序列的淋病奈瑟菌分离株中，9/76 株存在 501 位（A501V 或 A501T）取代，39/76 株存在 542 位取代，26/76 株存在 551 位取代。对之前研究中的 98 株淋病奈瑟菌分离株的重新分析表明，PBP2 542（G542S）和 551（P551S 或 P551L）处的取代与头孢曲松（P = 0.0186 和 0.001）和青霉素（P = 0.0231 和 0.0007）MIC 值升高显著相关。
我们的研究结果为 PBP2 G542S 和 P551S/P551L 参与对头孢曲松和青霉素的耐药性提供了有力证据。需要进一步研究来探讨这些突变的精确和相对作用。
