Two Multidrug-Resistant Clinical Isolates of Bacteroides fragilis Carry a Novel Metronidazole Resistance nim Gene (nimJ)
Two Multidrug-Resistant Clinical Isolates of Bacteroides fragilis Carry a Novel Metronidazole Resistance nim Gene (nimJ)
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DOI：
10.1128/aac.00386-13
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发表时间：
2013-08-01
影响因子：
4.9
通讯作者：
Wexler, Hannah M.
中科院分区：
文献类型：
--
作者：
Husain, Fasahath;Veeranagouda, Yaligara;Wexler, Hannah M.
两种多重耐药脆弱拟杆菌临床分离株含有并表达一种新的 nim 基因 nimJ，该基因不能被“通用”nim 引物识别，并且当通过多拷贝质粒导入易感菌株时，可以增强对甲硝唑的耐药性。 HMW615 是一种阑尾分离株，其基因组中至少含有两个 nimJ 拷贝，而 HMW616 是一种来自脓毒症患者的分离株，含有一个 nimJ 基因组拷贝。与其他已知的拟杆菌 Nim 蛋白相比，脆弱拟杆菌 NimJ 在系统发育上更接近巴氏普雷沃氏菌 NimI 和肉毒梭菌 NimA。基于折叠识别分析预测的 NimJ 蛋白质结构与已知 Nim 蛋白质的晶体结构一致，并且保留了对活性位点中的底物结合重要的特定氨基酸残基。这项研究表明，“通用”nim 引物不会检测到所有能够赋予甲硝唑耐药性的 nim 基因，但单独的 nimJ 无法解释这些耐药临床分离株的极高甲硝唑 MIC。
Two multidrug-resistant Bacteroides fragilis clinical isolates contain and express a novel nim gene, nimJ, that is not recognized by the "universal" nim primers and can confer increased resistance to metronidazole when introduced into a susceptible strain on a multicopy plasmid. HMW615, an appendiceal isolate, contains at least two copies of nimJ on its genome, while HMW616, an isolate from a patient with sepsis, contains one genomic copy of nimJ. B. fragilis NimJ is phylogenetically closer to Prevotella baroniae NimI and Clostridium botulinum NimA than to the other known Bacteroides Nim proteins. The predicted protein structure of NimJ, based on fold recognition analysis, is consistent with the crystal structures derived for known Nim proteins, and specific amino acid residues important for substrate binding in the active site are conserved. This study demonstrates that the "universal" nim primers will not detect all nim genes with the ability to confer metronidazole resistance, but nimJ alone cannot account for the very high metronidazole MICs of these resistant clinical isolates.