Glucose Absorption by the Bacillary Band of Trichuris muris.
Glucose Absorption by the Bacillary Band of Trichuris muris.
复制标题
DOI：
10.1371/journal.pntd.0004971
复制
发表时间：
2016-09
影响因子：
3.8
通讯作者：
Thamsborg SM
中科院分区：
文献类型：
--
作者：
Hansen TV;Hansen M;Nejsum P;Mejer H;Denwood M;Thamsborg SM
鞭虫属的一个共同特征。在人类和动物中的感染是可变的，但目前在针对人类鞭毛虫的大规模药物给药方案中使用的单剂量苯并咪唑的效力较低。鞭虫属的一种特殊形态结构--杆菌带，以及成年鞭虫属的独特的部分细胞内栖息地。可能影响药物吸收，并可能导致蠕虫中药物蓄积较低。然而，杆菌带的确切功能仍然未知。我们研究了成年鞭虫的依赖性，在体外生存的葡萄糖和/或氨基酸和菌带的吸收功能。使用0至3的运动量表评价蠕虫的活力，并使用比色测定Alcohol Blue测量代谢活性。用荧光葡萄糖类似物（6-NBDG）和共聚焦显微镜研究了活蠕虫菌带的吸收功能。为了研究与6-NBDG相关的杆菌带的吸收功能，通过用胶水和琼脂糖密封口腔来最小化或排除口腔摄取。葡萄糖对T的运动性（p < 0.001）和代谢活性（p < 0.001）均具有正效应。小鼠在体外，而这不是氨基酸的情况。6-NBDG被观察到的细菌带的孔和内stichocytes的活蠕虫，独立的口密封。鞭虫是依赖于葡萄糖的活力在体外，和杆菌带具有吸收功能的6-NBDG，其中积累的stichocytes。杆菌带的吸收功能要求探索其在吸收驱虫药中的可能作用，以及作为未来药物开发相关的潜在驱虫靶点。人类鞭虫Trichuris trichiura在许多热带和亚热带国家流行，据信感染了全球4.6亿多人。单剂量阿苯达唑或甲苯达唑治疗是目前人类鞭毛虫病的控制策略。然而，这种策略的治疗效果很差。已通过多种方式评估了治疗疗效低的原因，包括遗传分析以及体外和体内药理学研究。然而，这些研究尚未得出结论，也没有评价鞭虫属的生物学是否与人类的生殖系统有关。可能对治疗效果不佳产生影响。为了评估这一可能的原因，我们在这里探索一个专门的结构，命名为杆菌带的吸收功能。我们发现，葡萄糖被吸收的乐队和积累的蠕虫独立的口服摄入，我们推测，驱虫剂可能进入蠕虫通过相同的途径。如果是这样的话，这种新的见解可以用来优化目前和/或未来的驱虫药物在治疗人类鞭毛虫的药物配方。
A common characteristic of Trichuris spp. infections in humans and animals is the variable but low efficacy of single-dose benzimidazoles currently used in mass drug administration programmes against human trichuriasis. The bacillary band, a specialised morphological structure of Trichuris spp., as well as the unique partly intracellular habitat of adult Trichuris spp. may affect drug absorption and perhaps contribute to the low drug accumulation in the worm. However, the exact function of the bacillary band is still unknown. We studied the dependency of adult Trichuris muris on glucose and/or amino acids for survival in vitro and the absorptive function of the bacillary band. The viability of the worms was evaluated using a motility scale from 0 to 3, and the colorimetric assay Alamar Blue was utilised to measure the metabolic activity. The absorptive function of the bacillary band in living worms was explored using a fluorescent glucose analogue (6-NBDG) and confocal microscopy. To study the absorptive function of the bacillary band in relation to 6-NBDG, the oral uptake was minimised or excluded by sealing the oral cavity with glue and agarose. Glucose had a positive effect on both the motility (p < 0.001) and metabolic activity (p < 0.001) of T. muris in vitro, whereas this was not the case for amino acids. The 6-NBDG was observed in the pores of the bacillary band and within the stichocytes of the living worms, independent of oral sealing. Trichuris muris is dependent on glucose for viability in vitro, and the bacillary band has an absorptive function in relation to 6-NBDG, which accumulates within the stichocytes. The absorptive function of the bacillary band calls for an exploration of its possible role in the uptake of anthelmintics, and as a potential anthelmintic target relevant for future drug development. The human whipworm, Trichuris trichiura is prevalent in many tropical and subtropical countries and is believed to infect more than 460 million people worldwide. Treatment with single-dose albendazole or mebendazole is the current control strategy for human trichuriasis. This strategy, however, has a poor-to-mediocre treatment effect. The reason for the low treatment efficacy has been assessed in various ways, including genetic analysis, and both in vitro and in vivo pharmacological studies. However, these studies have not been conclusive and did not evaluate whether the biology of Trichuris spp. may have an impact on the inadequate treatment efficacy. To assess a possible reason for this, we here explore the absorptive function of a specialised structure, named the bacillary band. We found that glucose was absorbed by the band and accumulated within the worm independent of oral ingestion, and we speculate that anthelmintics may enter the worm by the same route. If this is the case, this new insight may be used to optimise drug formulations of current and/or future anthelmintic drugs in the treatment of human trichuriasis.
登录
查看更多内容
DOI：
10.1007/bf00329600
发表时间：
1972-01-01
期刊：
ZEITSCHRIFT FUR PARASITENKUNDE
影响因子：
--
作者：
JENKINS, T
通讯作者：
JENKINS, T
影响因子：
1.3
作者：
BRUCE, RG
通讯作者：
BRUCE, RG
影响因子：
11.8
作者：
Knopp, Stefanie;Mohammed, Khalfan A.;Utzinger, Juerg
通讯作者：
Utzinger, Juerg
DOI：
10.1111/j.1751-0813.1964.tb01660.x
发表时间：
1964-01-01
期刊：
AUSTRALIAN VETERINARY J
影响因子：
--
作者：
GORDON, H. McL.
通讯作者：
GORDON, H. McL.
DOI：
10.1111/j.1751-0813.1961.tb03921.x
发表时间：
1961-01-01
期刊：
AUSTRALIAN VET JOUR
影响因子：
--
作者：
HEBDEN, S. P.
通讯作者：
HEBDEN, S. P.