NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Key Laboratory of Respiratory Disease Pathogenomics, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Ann Clin Microbiol Antimicrob. 2023 Aug 17;22(1):73. doi: 10.1186/s12941-023-00614-x.
Antimicrobial resistance in gonorrhea has become a growing global public health burden. Neisseria gonorrhoeae isolates with resistance to ceftriaxone, the last remaining first-line option, represent an emerging threat of untreatable gonorrhea.
A total of ten ceftriaxone-resistant N. gonorrhoeae FC428 isolates and two isolates harboring a novel mosaic penA-232.001 allele from 160 gonococcal isolates in Chengdu in 2019-2020 was described in the present study. Multilocus sequence typing (MLST) and N. gonorrhoeae sequence typing for antimicrobial resistance (NG-STAR) were performed to characterize the isolates. Whole genome sequencing and maximum-likelihood method were performed to infer how the genetic phylogenetic tree of these isolates looks like. Recombination analysis was performed using the RDP4 software. This study was registered in the Chinese Clinical Trial Registry (ChiCTR2100048771, registration date: 20210716).
The genetic phylogeny showed that the ten FC428 isolates sporadically clustered into different phylogenetic clades, suggesting different introductions and local transmission of FC428. Two isolates showed close genetic relatedness to ceftriaxone-resistant clone A8806, which was only reported from Australia in 2013. Homologous recombination events were detected in penA between Neisseria gonorrhoeae and commensal Neisseria species (N. perflava and N. polysaccharea), providing evidence of commensal Neisseria species might serve as reservoirs of ceftriaxone resistance-mediating penA sequences in clinical gonococcal strains.
Our results demonstrate further dissemination of FC428 in China and resurgence risks of sporadic ceftriaxone-resistant A8806 to become the next clone to spread.
淋病中的抗菌药物耐药性已成为日益严重的全球公共卫生负担。对头孢曲松耐药的淋病奈瑟菌分离株,即最后一种尚存的一线治疗选择,代表了无法治愈淋病的新威胁。
本研究共描述了 2019 年至 2020 年来自成都的 160 例淋病奈瑟菌分离株中 10 株头孢曲松耐药的 FC428 分离株和 2 株携带新型嵌合 penA-232.001 等位基因的分离株。采用多位点序列分型(MLST)和淋病奈瑟菌耐药性序列分型(NG-STAR)对分离株进行特征描述。采用全基因组测序和最大似然法推断这些分离株的遗传系统发育树。采用 RDP4 软件进行重组分析。本研究在中国临床试验注册中心注册(ChiCTR2100048771,注册日期:20210716)。
遗传系统发育树显示,10 株 FC428 分离株散在聚集在不同的系统发育分支中,提示 FC428 存在不同的传入和局部传播。两株分离株与仅 2013 年在澳大利亚报道的头孢曲松耐药克隆 A8806 具有密切的遗传关系。在 penA 基因中检测到淋病奈瑟菌与共生奈瑟菌(奈瑟氏菌 perflava 和奈瑟氏菌 polysaccharea)之间的同源重组事件,这为共生奈瑟菌可能作为临床淋病奈瑟菌菌株中头孢曲松耐药调节 penA 序列的储库提供了证据。
我们的研究结果表明 FC428 在我国进一步传播,且散发性头孢曲松耐药 A8806 出现复燃风险,成为下一个传播的克隆。