Detection and quantification of Parascaris P-glycoprotein drug transporter expression with a novel mRNA hybridization technique
Detection and quantification of Parascaris P-glycoprotein drug transporter expression with a novel mRNA hybridization technique
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DOI：
10.1016/j.vetpar.2019.02.002
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发表时间：
2019-03-01
影响因子：
2.6
通讯作者：
Brewer, Matthew T.
中科院分区：
文献类型：
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作者：
Chelladurai, Jeba Jesudoss;Brewer, Matthew T.
大环内酯抗性寄生虫在世界各地都有报道。在某种程度上，耐药表型被假设与atp结合盒转运蛋白（p -糖蛋白）有关。在许多系统中，p -糖蛋白将药物排出细胞，从而阻止药物与靶受体结合。副蛔虫可能通过将药物从神经系统的靶受体外排而逃避大环内酯介导的死亡。或者，p糖蛋白在肠道或体壁的表达可以完全阻止药物渗透到寄生虫体内。在本研究中，我们使用一种新的多核酸杂交方法来评估peg -pgp-11和Peg-pgp-T-16的表达。该方法允许在成虫的固定组织切片中可视化单个mRNA转录物。结果表明，Peq-pgp-11和Peq-pgp-16在雌雄寄生虫的肠道、体壁、神经、侧索和生殖组织中均有表达。这些结果表明，Pgp可以在寄生虫神经组织水平局部外排药物，也可以在药物进入部位（如皮下和肠道）外排药物。多核酸杂交方法可以为多种线虫寄生虫的基因表达提供组织背景。
Macrocyclic lactone-resistant Parascaris have been reported throughout the world. In part, the drug resistant phenotype is hypothesized to be associated with ATP-binding cassette transporters known as P-glycoproteins. In many systems, P-glycoproteins efflux drugs out of cells thereby precluding drug binding to target receptors. Parascaris may evade macrocyclic lactone-mediated death by effluxing drugs away from target receptors in the nervous system. Alternatively, P-glycoprotein expression in the gut or body wall could prevent penetration of drugs into the body of the parasite altogether. In the present study, we evaluate expression of Peq-pgp-11 and Peg-pgp-T-16 using a novel multiple nucleic acid hybridization method. This method allowed for visualization of individual mRNA transcripts within fixed tissue sections of Parascaris adults. Our investigation revealed expression of Peq-pgp-11 and Peq-pgp-16 in the intestine, body wall, nerves, lateral cords, and reproductive tissues of male and female parasites. These results suggest that Pgp could efflux drugs locally at the level of parasite neuronal tissue as well as at sites of entry for drugs such as the hypodermis and intestine. The multiple nucleic acid hybridization method could be useful for providing tissue context for gene expression in a variety of nematode parasites.