Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark.
Department of Plant and Environmental Sciences, Faculty of Science, University of Copenhagen, Frederiksberg, Denmark.
PLoS Negl Trop Dis. 2016 Sep 2;10(9):e0004971. doi: 10.1371/journal.pntd.0004971. eCollection 2016 Sep.
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.
CONCLUSIONS/SIGNIFICANCE: 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.
人类和动物感染旋毛虫属的一个共同特征是，目前用于大规模药物管理方案的单一剂量苯并咪唑类药物对人体鞭虫病的疗效可变且较低。杆菌带是旋毛虫属的一种特殊形态结构，以及成年旋毛虫属的独特部分细胞内栖息地，可能会影响药物吸收，并且可能有助于减少蠕虫内药物的积累。然而，杆菌带的确切功能仍然未知。
我们研究了体外生存中，成年鼠旋毛虫对葡萄糖和/或氨基酸的依赖性，以及杆菌带的吸收功能。使用从 0 到 3 的运动量表评估蠕虫的活力，并利用比色法 Alamar Blue 测定代谢活性。使用荧光葡萄糖类似物（6-NBDG）和共焦显微镜研究活体蠕虫中杆菌带的吸收功能。为了研究杆菌带与 6-NBDG 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服摄取。
葡萄糖对 T. muris 的运动（p < 0.001）和代谢活性（p < 0.001）都有积极的影响，而氨基酸则不是这样。6-NBDG 被观察到在杆菌带的孔中和活体蠕虫的 Stichocytes 内，与口腔密封无关。
结论/意义：T. muris 在体外依赖葡萄糖存活，并且杆菌带具有与 6-NBDG 相关的吸收功能，6-NBDG 在 Stichocytes 内积累。杆菌带的吸收功能需要探索其在驱虫药物摄取中的可能作用，以及作为未来药物开发相关的潜在驱虫靶点。
