State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, 155 Changbai Road, Changping, Beijing, China.
BMC Microbiol. 2020 Mar 30;20(1):71. doi: 10.1186/s12866-020-01751-5.
Neisseria meningitidis (N.meningitidis) bacteria belonging to clonal complex 4821 (CC4821) have been mainly reported in China and have been characterized by a high resistance rate to ciprofloxacin (CIP). The aim of this study was to assess the evolution of the DNA gyrase A (gyrA) gene from N.meningitidis CC4821 strains collected in China between 1978 and 2016. The complete sequence of gyrA gene from 77 strains are reported in this study and analyzed in the context of publicly available sequences from N. meningitidis of other CCs as well as other Neisseria species.
The phylogenetic analysis of CC4821 gyrA gene reveals at least 5 distinct genetic clusters. These clusters are not CC4821-specific showing that gyrA evolution is independent of CC4821 evolution. Some clusters contain sequences from other Neisseria species. Recombination within N.meningitidis strains and between Neisseria species was identified in SimPlot analysis. Finally, amino acid substitutions within GyrA protein were analyzed. Only one position, 91 (83 in E.coli gyrA gene), was linked to CIP resistance. Thirty-one additional putative resistance markers were identified, as amino acid substitutions were only found in resistant strains.
The evolution of gyrA gene of CC4821 N.meningitidis strains is not dependent on CC4821 evolution or on CIP resistance phenotype. Only amino acid 91 is linked to CIP resistance phenotype. Finally, recombination inter- and intra-species is likely to result in the acquisition of various resistance markers, 31 of them being putatively mapped in the present study. Analyzing the evolution of gyrA gene within CC4821 strains is critical to monitor the CIP resistance phenotype and the acquisition of new resistance markers. Such studies are necessary for the control of the meningococcal disease and the development of new drugs targeting DNA gyrase.
属于克隆复合体 4821（CC4821）的脑膜炎奈瑟菌（N.meningitidis）细菌在中国主要有报道，其对环丙沙星（CIP）的耐药率较高。本研究旨在评估 1978 年至 2016 年间在中国采集的 CC4821 脑膜炎奈瑟菌株的 DNA 拓扑异构酶 A（gyrA）基因的进化情况。本研究报告了 77 株菌株 gyrA 基因的完整序列，并在公开的其他 CC 的脑膜炎奈瑟菌以及其他奈瑟菌属物种的序列背景下进行了分析。
CC4821 gyrA 基因的系统发育分析显示，至少存在 5 个不同的遗传簇。这些簇不是 CC4821 特异性的，表明 gyrA 进化独立于 CC4821 进化。一些簇包含来自其他奈瑟菌属物种的序列。SimPlot 分析鉴定了 N. meningitidis 菌株之间和奈瑟菌属物种之间的重组。最后，分析了 GyrA 蛋白中的氨基酸取代。只有一个位置 91（大肠杆菌 gyrA 基因中的 83）与 CIP 耐药性相关。还鉴定了 31 个额外的潜在耐药标记物，因为只有在耐药菌株中才发现氨基酸取代。
CC4821 脑膜炎奈瑟菌株 gyrA 基因的进化不依赖于 CC4821 进化或 CIP 耐药表型。只有氨基酸 91 与 CIP 耐药表型相关。最后，种间和种内重组可能导致各种耐药标记物的获得，其中 31 个标记物在本研究中被推测定位。分析 CC4821 菌株中 gyrA 基因的进化对于监测 CIP 耐药表型和获得新的耐药标记物至关重要。这些研究对于控制脑膜炎球菌病和开发靶向 DNA 拓扑异构酶的新药是必要的。
