灭滴灵抵抗幽门螺杆菌是由于空突变的基因(rdxA),编码一个oxygen-insensitive NADPH硝基还原酶。
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古德温,Kersulyte D, Sisson G, Veldhuyzen van Zanten SJ, Berg DE,霍夫曼PS
灭滴灵抵抗幽门螺杆菌是由于空突变的基因(rdxA),编码一个oxygen-insensitive NADPH硝基还原酶。
摩尔Microbiol。1998年4月28日(2):383 - 93。
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9622362 (在PubMed]
- 文摘
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灭滴灵(Mtz)是一个关键组成部分的联合疗法用于治疗幽门螺杆菌,消化性溃疡疾病的主要原因。许多幽门螺杆菌菌株耐Mtz (MtzR),但是,在这里,我们表明,MtzR结果失去oxygen-insensitive NADPH硝基还原酶的活动。潜在的基因(称为“rdxA”)被发现在几个步骤:转型Mtz-susceptible (MtzS)幽门螺旋杆菌与粘粒从MtzR应变,subcloning,聚合酶链反应(PCR)和DNA测序。我们还发现,(我)大肠杆菌(通常MtzR)由功能呈现MtzS幽门螺杆菌rdxA基因;(2)rdxA穿梭载体质粒上引入以前MtzR幽门螺旋杆菌呈现MtzS;和(3)更换rdxA MtzS幽门螺杆菌与rdxA:: camR零插入等位基因导致MtzR表现型。630 bp rdxA基因的5双幽门螺旋杆菌分离株(MtzR / MtzS)混合感染,但统一的整体基因型,测序。在每种情况下,配对rdxA基因不同于另一个替换由一至三个基地。典型rdxA基因在DNA序列无关的孤立相差5%。因此,附近的身份rdxA基因配对MtzR, MtzS隔离涉及新创突变,而不是水平基因转移在MtzR的发展。 Horizontal gene transfer could readily be demonstrated under laboratory conditions with mutant rdxA alleles. RdxA is a homologue of the classical nitroreductases (CNRs) of the enteric bacteria, but differs in cysteine content (6 vs. 1 or 2 in CNRs) and isoelectric point (pI=7.99 vs. 5.4-5.6), which might account for its reduction of low redox drugs such as Mtz. We suggest that many rdxA (MtzR) mutations may have been selected by prior use of Mtz against other infections. H. pylori itself is an early risk factor for gastric cancer; the possibility that its carcinogenic effects are exacerbated by Mtz use, which is frequent in many societies, or the reduction of nitroaromatic compounds to toxic, mutagenic and carcinogenic products, may be of significant concern in public health.