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红霉素体外诱导肺炎链球菌耐药的研究

, PP. 1185-1188

Keywords: 肺炎链球菌,红霉素,诱导,变异

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Abstract:

目的通过体外诱导获得肺炎链球菌(Streptococcuspneumoniae,S.pn)耐药菌株,对比分析S.pn诱导耐药前后红霉素结合域的变异。方法采用最低抑菌浓度(MIC)递增方法对S.pn标准菌株tigr4、tigr2临床分离敏感株进行红霉素体外诱导耐药,PCR与RT-PCR对诱导前后rplD、rplV基因以及23SrRNA扩增并测序,CPHmodels-2.0蛋白质空间构象预测系统对诱导前后rplD、rplV基因编码的核糖体蛋白L4和L22进行空间构象预测分析。结果诱导后tigr4MIC由0.0312mg/L增加到256mg/L,而临床分离敏感株MIC均由0.0312mg/L增加到32mg/L。诱导前后测序结果对比显示标准菌株tigr4核糖体蛋白L4发生V32A变异,L22发生D35G变异,而临床分离敏感株核糖体蛋白L4发生Q67R、K68E变异。空间构象分析L22的D35G及L4的Q67R、K68E变异导致其相应的表面空间构象发生明显改变。结论S.pn可通过红霉素体外诱导而导致耐药,其耐药机制与红霉素结合域发生新的变异有关。

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