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药物给药途径对天然产物桑拉辛 A 在斑马鱼胚胎感染模型中体内疗效的影响。

Impact of Drug Administration Routes on the In Vivo Efficacy of the Natural Product Sorangicin a Using a Infection Model in Zebrafish Embryos.

机构信息

Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), Saarland University, Campus E8 1, 66123 Saarbrücken, Germany.

German Centre for Infection Research (DZIF), Partner Site Hannover-Braunschweig, 38124 Braunschweig, Germany.

出版信息

Int J Mol Sci. 2023 Aug 14;24(16):12791. doi: 10.3390/ijms241612791.

Abstract

causes a wide range of infections, and it is one of the leading pathogens responsible for deaths associated with antimicrobial resistance, the rapid spread of which among urges the discovery of new antibiotics. The evaluation of in vivo efficacy of novel drug candidates is usually performed using animal models. Recently, zebrafish () embryos have become increasingly attractive in early drug discovery. Herein, we established a zebrafish embryo model of infection for evaluation of in vivo efficacy of novel potential antimicrobials. A local infection was induced by microinjecting mCherry-expressing Newman followed by treatment with reference antibiotics via microinjection into different injection sites as well as via waterborne exposure to study the impact of the administration route on efficacy. We successfully used the developed model to evaluate the in vivo activity of the natural product sorangicin A, for which common mouse models were not successful due to fast degradation in plasma. In conclusion, we present a novel screening platform for assessing in vivo activity at the antibiotic discovery stage. Furthermore, this work provides consideration for the choice of an appropriate administration route based on the physicochemical properties of tested drugs.

摘要

导致了广泛的感染,并且是与抗菌药物耐药性相关死亡的主要病原体之一,其在之间的迅速传播促使人们发现新的抗生素。新型候选药物的体内疗效评估通常使用动物模型进行。最近,斑马鱼()胚胎在早期药物发现中变得越来越有吸引力。在此,我们建立了一个斑马鱼胚胎模型,用于评估新型潜在抗菌药物的体内疗效。通过微注射表达 mCherry 的 Newman 诱导局部感染,然后通过微注射到不同注射部位以及通过水暴露来用参考抗生素进行处理,以研究给药途径对疗效的影响。我们成功地使用该模型评估了天然产物 sorangicin A 的体内活性,由于其在血浆中快速降解,常见的小鼠模型并不成功。总之,我们提出了一种新的筛选平台,用于在抗生素发现阶段评估体内活性。此外,这项工作还考虑了根据测试药物的物理化学性质选择合适的给药途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b57/10454396/59256444a3b6/ijms-24-12791-g001.jpg

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