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中国 Y 群血清型 23 型克隆复合体脑膜炎奈瑟菌从共生奈瑟菌属获得青霉素耐药性。

Serogroup Y Clonal Complex 23 Meningococcus in China Acquiring Penicillin Resistance from Commensal Neisseria lactamica Species.

机构信息

Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, People's Republic of China.

Key Laboratory of Clinical Pharmacology of Antibiotics, National Heath Commission of the People's Republic of China, Shanghai, People's Republic of China.

出版信息

Antimicrob Agents Chemother. 2022 Jun 21;66(6):e0238321. doi: 10.1128/aac.02383-21. Epub 2022 Jun 2.

Abstract

Invasive meningococcal disease (IMD) due to serogroup Y Neisseria meningitidis (NmY) is rare in China; recently, an invasive NmY isolate, Nm512, was discovered in Shanghai with decreased susceptibility to penicillin (Pen). Here, we investigated the epidemiology of NmY isolates in Shanghai and explored the potential commensal Neisseria lactamica donor of the Pen NmY isolate. A total of 491 N. meningitidis and 724 commensal spp. isolates were collected. Eleven NmY isolates were discovered from IMD ( = 1) and carriers ( = 10), including two Pen isolates with five-key-mutation-harboring (F504L-A510V-I515V-H541N-I566V) genes. Five of the eight ST-175 complex (CC175) isolates had a genotype [Y:P1.5-1,2-2:F5-8:ST-175(CC175)] identical to that of the predominant invasive clone found in South Africa. Only one invasive NmY CC23 isolate (Nm512) was discovered; this isolate carried a novel Pen allele, which was identified in commensal N. lactamica isolates locally. Recombination analysis and transformation of the allele highlighted that N. meningitidis Nm512 may acquire resistance from its commensal donor; this was supported by the similar distribution of transformation-required DNA uptake sequence variants and the highly cognate receptor ComP between N. meningitidis and N. lactamica. In 2,309 NmY CC23 genomes from the PubMLST database, isolates with key-mutation-harboring genes comprised 12% and have been increasing since the 1990s, accompanied by recruitment of the and/or quinolone resistance allele. Moreover, was predominant among genomes without key mutations in . These results strongly suggest that Nm512 is a descendant of the -harboring CC23 isolate from Europe and acquired its penicillin resistance locally from commensal N. lactamica species by natural transformation.

摘要

中国罕见由血清群 Y 脑膜炎奈瑟菌(NmY)引起的侵袭性脑膜炎奈瑟氏菌病(IMD);最近,在上海发现了一种具有降低青霉素(Pen)敏感性的侵袭性 NmY 分离株 Nm512。在这里,我们研究了上海 NmY 分离株的流行病学,并探讨了 Pen NmY 分离株潜在的共生奈瑟氏菌 lactamica 供体。共收集了 491 株脑膜炎奈瑟菌和 724 株共生 分离株。从 IMD( = 1)和携带者( = 10)中发现了 11 株 NmY 分离株,包括两株携带五个关键突变基因(F504L-A510V-I515V-H541N-I566V)的 Pen 分离株。八个 ST-175 复合物(CC175)分离株中有 5 个具有与南非发现的主要侵袭性克隆相同的基因型[Y:P1.5-1,2-2:F5-8:ST-175(CC175)]。仅发现了一种侵袭性 NmY CC23 分离株(Nm512);该分离株携带一种新型的 Pen 等位基因,该等位基因在当地的共生奈瑟氏菌 lactamica 分离株中被发现。重组分析和 等位基因的转化突出表明,Nm512 可能从其共生供体中获得了耐药性;这得到了脑膜炎奈瑟氏菌和奈瑟氏菌 lactamica 之间转化所需的 DNA 摄取序列变体和高度同源受体 ComP 的相似分布的支持。在 PubMLST 数据库中的 2309 株 NmY CC23 基因组中,携带关键突变基因的分离株占 12%,自 20 世纪 90 年代以来一直在增加,同时招募了 和/或喹诺酮耐药等位基因。此外,在没有关键突变的基因组中, 占主导地位。这些结果强烈表明,Nm512 是来自欧洲的携带 基因的 CC23 分离株的后代,通过自然转化从当地的共生奈瑟氏菌 lactamica 物种中获得了青霉素耐药性。

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