Department of Microbiology and Infectious Diseases, Toho University Graduate School of Medicine, Tokyo, Japan.
Department of Medical Technology, Faculty of Health Science, Tokyo University of Technology, Tokyo, Japan.
J Antimicrob Chemother. 2021 Jun 18;76(7):1769-1775. doi: 10.1093/jac/dkab104.
To investigate the spread of ceftriaxone-resistant Neisseria gonorrhoeae lineages similar to strains H041 (2009) and FC428 (2015), we characterized 55 strains collected in 2013 from hospitals across Japan.
Susceptibility testing and whole-genome sequencing.
Susceptibility rates were 58% for cefixime and 98% for ceftriaxone. The 55 strains were whole-genome sequenced and classified into nine MLST-STs. MLST-ST1901 was the most prevalent (n = 19) followed by MLST-ST7363 (n = 12) and MLST-ST7359 (n = 11). The most prevalent penA [encoding penicillin binding protein 2 (PBP2)] mosaic types, based on the N. gonorrhoeae sequence typing for antimicrobial resistance (NG-STAR) scheme, were 10.001 (n = 20) followed by 34.001 (n = 13). The H041 and FC428 strains were not detected; however, a single ceftriaxone-resistant strain (TUM15748) with a MIC of 0.5 mg/L ceftriaxone was identified. The TUM15748 strain belonged to MLST-ST7359 and N. gonorrhoeae multiantigen sequence typing-ST6771, and had a novel PBP2 (PBP2TUM15748, penA type 169.001). The amino acid sequence of PBP2TUM15748 showed partial similarity to that of PBP2 from N. gonorrhoeae GU140106 and commensal Neisseria perflava and Neisseria cinerea. Natural transformation and recombination experiments using full-length TUM15748 penA showed that the ceftriaxone MICs of transformants increased 16-fold or more compared with the parental ceftriaxone-susceptible recipient strain (NG9807, belonging to MLST-ST7363). No ceftriaxone-resistant MLST-ST7359 strains have previously been reported.
We showed here that a ceftriaxone-susceptible lineage acquired a mutant PBP2 mosaic type, integrating partial PBP2 sequences from commensal Neisseria species, resulting in the emergence of ceftriaxone-resistant strains.
为了研究与 H041（2009 年）和 FC428（2015 年）菌株相似的头孢曲松耐药淋病奈瑟菌谱系的传播情况，我们对 2013 年从日本各地医院采集的 55 株菌株进行了特征描述。
药敏试验和全基因组测序。
头孢克肟的药敏率为 58%，头孢曲松的药敏率为 98%。55 株菌株进行了全基因组测序，并分为 9 种 MLST-ST。MLST-ST1901 最为常见（n=19），其次是 MLST-ST7363（n=12）和 MLST-ST7359（n=11）。根据淋病奈瑟菌耐药性序列分型（NG-STAR）方案，最常见的 penA[编码青霉素结合蛋白 2（PBP2）]嵌合类型是 10.001（n=20），其次是 34.001（n=13）。未检测到 H041 和 FC428 菌株；然而，鉴定出了一株头孢曲松耐药株（TUM15748），其头孢曲松 MIC 为 0.5mg/L。TUM15748 株属于 MLST-ST7359 和淋病奈瑟菌多抗原序列分型-ST6771，具有新型 PBP2（PBP2TUM15748，penA 类型 169.001）。PBP2TUM15748 的氨基酸序列与淋病奈瑟菌 GU140106 和共生奈瑟菌和奈瑟菌 cinerea 的 PBP2 具有部分相似性。使用全长 TUM15748 penA 进行自然转化和重组实验表明，与亲本头孢曲松敏感受体株（NG9807，属于 MLST-ST7363）相比，转化体的头孢曲松 MIC 增加了 16 倍或更多。以前没有报道过头孢曲松敏感的 MLST-ST7359 菌株。
我们在这里表明，一种头孢曲松敏感的谱系获得了一种突变的 PBP2 嵌合类型，整合了来自共生奈瑟菌属物种的部分 PBP2 序列，导致头孢曲松耐药菌株的出现。
