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耐异烟肼结核分支杆菌相关耐药基因突变研究

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摘要 目的 阐明结核分支杆菌耐异烟肼临床分离株katG、inhA、ahpC、kasA及oxyR基因突变特点.方法 对144株结核分支杆菌临床分离株(101株耐异烟肼株,43株敏感株)katG,inhA kasA及oxyR基因进行DNA序列分析。结果 ①耐异烟肼株中未发现katG完全缺失。共检测到80.20%(81/101)的菌株存在点突变、缺失或插入,其中16个突变位点未见过报道,38.61%(39/101)的耐药菌株315位点突变。结合菌株耐药程度,低耐药组(≥1μg/ml)315位点突变率显著高于高耐药组(≥10μg/ml)315位点突变率(P<0.05)。57.43%(58/101)的耐异烟肼菌株存在463位点突变。其它位点发生突变的菌株为15.84%(16/101)株。53.49%(23/43)的敏感株463位点突变;②耐异烟肼株中共有4.95%(5/101)株inhA发生突变。敏感株中没有检测到inhA突变;③耐异烟肼株中共有3株(2.97%)ahpC有突变,均为高度耐药。敏感株中没有检测到ahpC基因突变。④耐异烟肼株中共有16.83%(17/101)株发生KasA突变,均为低度耐药。敏感株中检测到3株细菌存在G312S突变;⑤在144株临床分离株中未发现oxyR基因突变;⑥综合本项研究中katG、inhA、ahpC及kasA基因的突变情况,共有85株耐异烟肼菌株发生与异烟肼耐药相关的突变(katG67株、inhA5株、ahpC3株、kasA10株),占84%(85/101)。结论 本项研究进一步证实了结核分支杆菌耐异烟肼与katG,inhA,ahpC,kasA基因突变之间的关系,并且提示可能存在其它尚未阐明的机制参与异烟肼耐药。
出处 《结核病与胸部肿瘤》 2004年第1期23-33,共11页 Tuberculosis and Thoracic Tumor
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