Emergence and spread of Neisseria gonorrhoeae clinical isolates harboring mosaic-like structure of penicillin-binding protein 2 in central Japan
Emergence and spread of Neisseria gonorrhoeae clinical isolates harboring mosaic-like structure of penicillin-binding protein 2 in central Japan
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DOI：
10.1128/aac.49.1.137-143.2005
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发表时间：
2005-01-01
影响因子：
4.9
通讯作者：
Ezaki, T
中科院分区：
文献类型：
--
作者：
Ito, M;Deguchi, T;Ezaki, T
在2001年分离出的150株淋病奈瑟菌临床菌株中，我们检测了55株头孢克肟最低抑菌浓度（MIC）≥0.125μg/ml的淋病奈瑟菌临床菌株，并随机选取了15株头孢克肟MIC≤0.06μg/ml的菌株，用于分析青霉素结合蛋白2（PBP 2）基因的改变。我们发现PBP 2的转肽酶结构域中插入了一个额外的密码子（天冬氨酸 - 345a），这种插入单独发生或与其他氨基酸替换同时发生。我们还发现了一种嵌合的PBP 2，它由灰色奈瑟菌和浅黄奈瑟菌的PBP 2蛋白片段组成。这种嵌合的PBP 2与对青霉素和头孢菌素，尤其是口服头孢菌素的敏感性降低显著相关。对于大多数具有嵌合PBP 2的菌株，头孢克肟MIC≥0.5μg/ml，头孢地尼MIC≥1μg/ml。通过脉冲场凝胶电泳对染色体DNA限制图谱的分析显示，大多数具有嵌合PBP 2的菌株在基因上相似。产生嵌合PBP 2的重组事件可能导致了对头孢菌素敏感性的降低。具有嵌合PBP 2的菌株似乎威胁到目前推荐的头孢克肟治疗方案的疗效。这类菌株的出现可能是淋病奈瑟菌的penA基因与共生奈瑟菌属物种之间发生种间重组的克隆在体内产生的结果。
Of 150 clinical isolates of Neisseria gonorrhoeae recovered in 2001, we examined 55 clinical isolates of N. gonorrhoeae for which cefixime MICs were greater than or equal to0.125 mug/ml and randomly selected 15 isolates for which cefixime MICs were less than or equal to0.06 mug/ml for analysis of alterations in the penicillin-binding protein 2 (PBP 2) gene. We found insertion of an extra codon (Asp-345a) in the transpeptidase domain of PBP 2, and this insertion occurred alone or in conjunction with other amino acid substitutions. We also found a mosaic PBP 2 that was composed of fragments of the PBP 2 proteins from Neisseria cinera and Neisseria perflava. This mosaic PBP 2 was significantly associated with decreased susceptibilities to penicillin and cephalosporins, especially oral cephalosporins. For most of the isolates with a mosaic PBP 2, the cefixime MICs were greater than or equal to0.5 mug/ml and the cefdinir MICs were greater than or equal to1 mug/ml. Analysis of chromosomal DNA restriction patterns by pulsed-field gel electrophoresis revealed that most isolates with the mosaic PBP 2 were genetically similar. The recombination events that generated the mosaic PBP 2 would likely have contributed to the decreased sensitivities to cephalosporins. Isolates with the mosaic PBP 2 appear to threaten the efficacy of the currently recommended regimen with cefixime. The emergence of such strains may be the result of the in vivo generation of clones in which interspecies recombination occurred between the penA genes of N. gonorrhoeae and commensal Neisseria species.