Repertoire of P-glycoprotein drug transporters in the zoonotic nematode Toxocara canis.
Repertoire of P-glycoprotein drug transporters in the zoonotic nematode Toxocara canis.
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人畜共患毒素toxocara canis中P-糖蛋白药物转运蛋白的曲目。
DOI：
10.1038/s41598-023-31556-1
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发表时间：
2023-03-27
影响因子：
4.6
通讯作者：
Brewer, Matthew T.
中科院分区：
文献类型：
--
作者：
Chelladurai, Jeba R. J. Jesudoss;Martin, Katy A.;Vardaxis, Pam;Reinemeyer, Craig;Vijayapalani, Paramasivan;Robertson, Alan P.;Brewer, Matthew T.
犬弓形虫有一个复杂的生活史，包括耐受大环内酯的犬的躯体组织中的幼虫阶段。在这项研究中，我们研究了犬弓形虫通透性糖蛋白(P-GPS，ABCB1)在药物耐受性中的可能作用。运动实验表明，虽然伊维菌素不能阻止幼虫的运动，但伊维菌素与P-gp抑制剂维拉帕米联合使用可导致幼虫瘫痪。整个生物体检测表明，幼虫体内有功能的P-gp活性，能够分泌P-gp底物Hoechst 33342(H33342)。对H33342外排的进一步研究表明，已知的哺乳动物P-gp抑制剂的效力具有独特的等级顺序，这表明一个或多个犬旋毛虫转运蛋白具有线虫特有的药理特性。对犬毛滴虫草稿基因组的分析得到了13个带注释的P-gp基因的鉴定，从而能够修改预测的基因名称和鉴定可能的并列基因。用定量聚合酶链式反应检测P-gp在成虫、孵化幼虫和体细胞幼虫中的表达。至少有10个预测基因在成虫和孵化的幼虫中表达，至少8个在体细胞幼虫中表达。然而，用大环内酯类化合物处理幼虫并不能显著增加P-gp的表达。需要进一步的研究来了解个体P-GPS在犬毛滴虫大环内酯耐受性中的作用。
Toxocara canis has a complex lifecycle including larval stages in the somatic tissue of dogs that tolerate macrocyclic lactones. In this study, we investigated T. canis permeability glycoproteins (P-gps, ABCB1) with a putative role in drug tolerance. Motility experiments demonstrated that while ivermectin failed to abrogate larval movement, the combination of ivermectin and the P-gp inhibitor verapamil induced larval paralysis. Whole organism assays revealed functional P-gp activity in larvae which were capable of effluxing the P-gp substrate Hoechst 33342 (H33342). Further investigation of H33342 efflux demonstrated a unique rank order of potency for known mammalian P-gp inhibitors, suggesting that one or more of the T. canis transporters has nematode-specific pharmacological properties. Analysis of the T. canis draft genome resulted in the identification of 13 annotated P-gp genes, enabling revision of predicted gene names and identification of putative paralogs. Quantitative PCR was used to measure P-gp mRNA expression in adult worms, hatched larvae, and somatic larvae. At least 10 of the predicted genes were expressed in adults and hatched larvae, and at least 8 were expressed in somatic larvae. However, treatment of larvae with macrocyclic lactones failed to significantly increase P-gp expression as measured by qPCR. Further studies are needed to understand the role of individual P-gps with possible contributions to macrocyclic lactone tolerance in T. canis.
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影响因子：
3.2
作者：
Durant JF;Irenge LM;Fogt-Wyrwas R;Dumont C;Doucet JP;Mignon B;Losson B;Gala JL
通讯作者：
Gala JL
影响因子：
4
作者：
GILL, JH;REDWIN, JM;LACEY, E
通讯作者：
LACEY, E
影响因子：
3.7
作者：
Jesudoss Chelladurai, Jeba R. J.;Martin, Katy A.;Brewer, Matthew T.
通讯作者：
Brewer, Matthew T.
影响因子：
2
作者：
Bader, Chris;Chelladurai, Jeba Jesudoss;Brewer, Matthew T.
通讯作者：
Brewer, Matthew T.
DOI：
10.1111/j.1439-0450.2006.00948.x
发表时间：
2006-06-01
期刊：
JOURNAL OF VETERINARY MEDICINE SERIES B-INFECTIOUS DISEASES AND VETERINARY PUBLIC HEALTH
影响因子：
--
作者：
Kraemer, F.;Hammerstein, R.;Epe, C.
通讯作者：
Epe, C.