Allen Nathan Rhys, Huson Kathryn M, Prchal Lukas, Robinson Mark W, Brophy Peter M, Morphew Russell M
Department of Life Sciences, Aberystwyth University, Aberystwyth, Wales SY23 3DA, U.K.
School of Biological Sciences, Queen's University Belfast, Belfast, Northern Ireland BT9 5BY, U.K.
J Proteome Res. 2025 Feb 7;24(2):624-638. doi: 10.1021/acs.jproteome.4c00615. Epub 2025 Jan 19.
Helminth parasites have long adapted to survive hostile host environments and can likely adapt against the chemical anthelmintic challenge. One proposed adaptation route is via Phase I and II xenobiotic metabolizing enzymes (XMEs). For successful Helminth pharmacotherapy discovery programs, a working understanding of Helminth-derived chemical detoxification, the Helminth detoxome, is a must. At present, the detoxome of a newly emerging Helminth parasite, the rumen fluke , remains unexplored. Thus, a combined bioinformatics, sub-, and global-proteomic approach has been employed to examine the detoxome of adult . Transcriptome analysis revealed a complement of Phase I (cytochrome P450s and monoamine oxygenases) and Phase II (glutathione transferases [GSTs] and sulfotransferases) XMEs. Affinity-led subproteomic exploration of the GSTs revealed six GST isoforms in adult rumen fluke (CdGST-Mu1-2, S1, and S3-5), with global approaches identifying additional GSTs (CdGST-O1-2, Z1, and S2) and a unique egg-specific variant (CdGST-S6). Examination of extracellular vesicles revealed a GST profile replicating that of the adult with the absence of two isoforms (CdGST-S2 and S4), with an additional identification of a sulfotransferase. These data represent the first exploration into the complete rumen fluke detoxification capacity and will provide direction for future anthelmintic discovery programs.
蠕虫寄生虫长期以来一直在适应在恶劣的宿主环境中生存，并且很可能能够适应化学驱虫剂的挑战。一种提出的适应途径是通过I相和II相异生物质代谢酶（XMEs）。对于成功的蠕虫药物治疗发现计划而言，必须对蠕虫衍生的化学解毒作用（即蠕虫解毒组）有切实的了解。目前，一种新出现的蠕虫寄生虫——瘤胃吸虫的解毒组仍未被探索。因此，已采用生物信息学、亚蛋白质组学和全局蛋白质组学相结合的方法来研究成年瘤胃吸虫的解毒组。转录组分析揭示了I相（细胞色素P450和单胺氧化酶）和II相（谷胱甘肽转移酶[GSTs]和磺基转移酶）XMEs的一个补充。对GSTs进行的基于亲和的亚蛋白质组学探索揭示了成年瘤胃吸虫中的六种GST同工型（CdGST-Mu1-2、S1和S3-5），全局方法鉴定出了其他GSTs（CdGST-O1-2、Z1和S2）以及一种独特的卵特异性变体（CdGST-S6）。对细胞外囊泡的检测显示，其GST谱与成虫的谱相似，但缺少两种同工型（CdGST-S2和S4），另外还鉴定出了一种磺基转移酶。这些数据代表了对瘤胃吸虫完整解毒能力的首次探索，并将为未来的驱虫剂发现计划提供指导。
