Development of in vitro atovaquone-resistant Babesia gibsoni with a single-nucleotide polymorphism in cytb
Development of in vitro atovaquone-resistant Babesia gibsoni with a single-nucleotide polymorphism in cytb
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DOI：
10.1016/j.vetpar.2011.09.031
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发表时间：
2012-04-30
影响因子：
2.6
通讯作者：
Hikasa, Yoshiaki
中科院分区：
文献类型：
--
作者：
Iguchi, Aiko;Matsuu, Aya;Hikasa, Yoshiaki
通过体外暴露未克隆的野生型（WT）B，培育了阿托伐醌（ATV）抗性吉氏巴氏巴氏杆菌。gibsoni与800 nM ATV接触6天。线粒体基因的序列分析显示cytb nt363（G至T）处的单核苷酸多态性（SNP），导致蛋氨酸被异亮氨酸（M121 I）取代，这是先前体内研究中报道的SNP之一。363T或363G等位基因特异性实时聚合酶链反应（PCR）显示，超过99%的ATV耐药人群中存在M121 I变异。由于B群体既未出现ATV抗性，也未出现基因多态性。gibsoni WT同胞克隆中，本研究中ATV抗性的表达被怀疑是因为B的选择性增殖。吉布森M121I变种这种抗ATV的B. gibsoni显示出与WT B相同的敏感性。Gibsoni对其他5种药物，包括醋氨酰亚胺、阿奇霉素、强力霉素、克林霉素和氯胍。这是第一次在体外建立抗ATV的B。gibsoni基因多态性。(C)2011爱思唯尔有限公司版权所有。
An atovaquone (ATV)-resistant Babesia gibsoni was developed by in vitro exposure of uncloned wild type (WT) B. gibsoni to 800 nM ATV for 6 days. Sequence analysis of mitochondria] genes showed a single-nucleotide polymorphism (SNP) at cytb nt363 (G to T) that resulted in the substitution of methionine with isoleucine (M121I), which is one of the SNPs reported in a previous in vivo study. 363T or 363G allele-specific real-time polymerase chain reaction (PCR) revealed that an M121I variant was present in over 99% of the ATV-resistant population. As neither ATV resistance nor gene polymorphisms appeared in the B. gibsoni WT sibling clones, the expression of ATV resistance in this study was suspected to be because of selective multiplication of the B. gibsoni M121I variant. This ATV-resistant B. gibsoni displayed the same sensitivity as the WT B. gibsoni against 5 other drugs, including diminazene aceturate, azithromycin, doxycycline, clindamycin, and proguanil. This is the first report on the in vitro establishment of an ATV-resistant B. gibsoni with gene polymorphisms. (C) 2011 Elsevier B.V. All rights reserved.