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结核分枝杆菌thyA基因突变与对氨基水杨酸钠耐药关系的研究 被引量:4

Relationship between gene thyA mutation with para-aminosalicylic acid resistance in Mycobacterium tuberculosis
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摘要 目的了解Mtb临床分离菌株中对于对氨基水杨酸钠(PAS)的耐药率及PAS耐药性与thyA基因突变的关系。方法从肺结核患者的痰标本中分离并鉴定Mtb 96株,采用比例法、全基因测序的方法检测上述Mtb临床菌株对PAS的耐药性情况及其thyA基因突变情况。结果 96株Mtb中,65株为PAS敏感菌株和31株为PAS耐药菌株。以Mtb标准菌株H37Rv为对照,筛选敏感和耐药菌株中的thyA基因突变率分别是46.15%(30/65)、70.97%(22/31),突变多为单个碱基的缺失和插入突变,其中又以第19位密码子缺失C、第168位密码子缺失C为主,在耐药中所占比率分别是54.84%(17/31)、25.81%(8/31),其在敏感菌株中的比率也分别是35.38%(23/65)、12.31%(8/65)。结论耐药菌株中thyA基因的突变频率明显高于敏感菌株,thyA基因可能是PAS耐药潜在靶点,但未发现其特异性突变位点。 Objective To study para-aminosalicylic acid (PAS) resistance rates in M. tuberculosis isolates and the relationship with thyA gene mutation. Methods Ninety-six M. tuberculosis strains were isolated and iden tiffed from the sputa or ttaroat swab specimens of tuberculosis patients. M. tuberculosis strains resistance to PAS was determined by the proportional method, and their thyA gene mutation was detected by PCR-DNA sequencing. Results Of 96 M. tuberculosis isolates, 65 were PAS-sensitive, and 31 were PAS-resistant. Using M. tuberculosis H37Rv as a control, the thyA gene mutation rate in PAS-sensitive and PAS-resistant strains of M. tuberculosis were 46.15~ (30/65) and 70. 97~ (22/31), respectively. Most of stains showed single base deletion and insertion mu tations, in which C deletion at codon 19 and codon 168 were 54.84% (17/31), 25.81% (8/31) in PAS-resistant stains respectively, and 35.38% (23/65) and 12.31% (8/65) in PAS-sensitive strains respectively. Conclusion The frequency of the thyA gene mutation in PAS-resistant strains was significantly higher than that in PAS-sensitive strains. The thyA gene could be a potential target for the development of PAS resistance. But there were not. any site with specific mutation found in this study.
出处 《中国防痨杂志》 CAS 2012年第6期350-353,共4页 Chinese Journal of Antituberculosis
基金 首都医学发展科研基金(2009-1055)
关键词 分枝杆菌 结核 对氨基水杨酸钠 抗药性 细菌 胸苷酸合酶 Mycobacterium tuberculosis p-Aminosalicyclic acid Drug resistance, bacterial Thymidylate synthase
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参考文献13

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二级参考文献4

  • 1中国防痨协会基础专业委员会.结核病诊断实验室检验规程.北京:中国教育出版社,2006,46-51.
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  • 4Rengarajan J, Sassetti CM, Naroditskaya V, et al. The folate pathway is a target for resistance to the drug para-aminosalicylic acid (PAS) in mycobacteria. Mol Microbiol, 2004,53:275-282.

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