Golparian Daniel, Jacobsson Susanne, Sánchez-Busó Leonor, Bazzo Maria Luiza, Lan Pham Thi, Galarza Patricia, Ohnishi Makoto, Unemo Magnus
Department of Laboratory Medicine, Microbiology, Faculty of Medicine and Health, WHO Collaborating Centre for Gonorrhoea and Other Sexually Transmitted Infections, Örebro University, Örebro, Sweden.
Genomics and Health Area, Foundation for the Promotion of Health and Biomedical Research in the Valencian Community (FISABIO-Public Health), Valencia, Spain and Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain.
J Antimicrob Chemother. 2022 Dec 23;78(1):150-154. doi: 10.1093/jac/dkac366.
Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is a global threat and novel treatment alternatives are imperative. Herein, susceptibility to the novel antimicrobial zoliflodacin, currently in a global Phase 3 randomized controlled clinical trial for gonorrhoea treatment, was investigated by screening for zoliflodacin GyrB target mutations in publicly available gonococcal genomes and, where feasible, determination of the associated zoliflodacin MIC.
The European Nucleotide Archive was queried using the search term 'Taxon: 485'. DNA sequences from 27 151 gonococcal isolates were analysed and gyrB, gyrA, parC and parE alleles characterized.
GyrB amino acid alterations were rare (97.0% of isolates had a wild-type GyrB sequence). GyrB V470L (2.7% of isolates) was the most prevalent alteration, followed by S467N (0.12%), N. meningitidis GyrB (0.092%), V470I (0.059%), Q468R/P (0.015%), A466T (0.0074%), L425I + L465I (0.0037%), L465I (0.0037%), G482S (0.0037%) and D429V (0.0037%). Only one isolate (0.0037%) carried a substitution in a resistance-associated GyrB codon (D429V), resulting in a zoliflodacin MIC of 8 mg/L. None of the other detected gyrB, gyrA, parC or parE mutations caused a zoliflodacin MIC outside the wild-type MIC distribution.
The zoliflodacin target GyrB was highly conserved among 27 151 global gonococcal isolates cultured in 1928-2021. The single zoliflodacin-resistant clinical isolate (0.0037%) was cultured from a male patient in Japan in 2000. Evidently, this strain has not clonally expanded nor has the gyrB zoliflodacin-resistance mutation disseminated through horizontal gene transfer to other strains. Phenotypic and genomic surveillance, including gyrB mutations, of zoliflodacin susceptibility are imperative.
淋病奈瑟菌的抗菌药物耐药性（AMR）是一项全球性威胁，因此迫切需要新的治疗选择。本文通过在公开可用的淋球菌基因组中筛查唑利弗达辛GyrB靶点突变，并在可行的情况下测定相关的唑利弗达辛最低抑菌浓度（MIC），对目前正在进行全球3期淋病治疗随机对照临床试验的新型抗菌药物唑利弗达辛的敏感性进行了研究。
使用搜索词“分类单元：485”查询欧洲核苷酸档案库。分析了来自27151株淋球菌分离株的DNA序列，并对gyrB、gyrA、parC和parE等位基因进行了特征分析。
GyrB氨基酸改变很少见（97.0%的分离株具有野生型GyrB序列）。GyrB V470L（占分离株的2.7%）是最常见的改变，其次是S467N（0.12%）、脑膜炎奈瑟菌GyrB（0.092%）、V470I（0.059%）、Q468R/P（0.015%）、A466T（0.0074%）、L425I + L465I（0.0037%）、L465I（0.0037%）、G482S（0.0037%）和D429V（0.0037%）。只有一株分离株（0.0037%）在与耐药相关的GyrB密码子中发生了替换（D429V），导致唑利弗达辛MIC为8 mg/L。其他检测到的gyrB、gyrA、parC或parE突变均未导致唑利弗达辛MIC超出野生型MIC分布范围。
在1928年至2021年培养的27151株全球淋球菌分离株中，唑利弗达辛靶点GyrB高度保守。这株对唑利弗达辛耐药的临床分离株（0.0037%）于2000年从日本一名男性患者中分离得到。显然，该菌株没有进行克隆性扩增，gyrB唑利弗达辛耐药突变也没有通过水平基因转移传播到其他菌株。对唑利弗达辛敏感性进行表型和基因组监测，包括gyrB突变监测，势在必行。
