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利用新优化的遗传工具来探究钩虫的感觉行为。

Using newly optimized genetic tools to probe Strongyloides sensory behaviors.

机构信息

Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA; Molecular Biology Interdepartmental PhD Program, University of California Los Angeles, Los Angeles, CA, USA.

Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA; Molecular Biology Interdepartmental PhD Program, University of California Los Angeles, Los Angeles, CA, USA; Medical Scientist Training Program, University of California, Los Angeles, Los Angeles, CA, USA.

出版信息

Mol Biochem Parasitol. 2022 Jul;250:111491. doi: 10.1016/j.molbiopara.2022.111491. Epub 2022 Jun 10.

Abstract

The oft-neglected human-parasitic threadworm, Strongyloides stercoralis, infects roughly eight percent of the global population, placing disproportionate medical and economic burden upon marginalized communities. While current chemotherapies treat strongyloidiasis, disease recrudescence and the looming threat of anthelminthic resistance necessitate novel strategies for nematode control. Throughout its life cycle, S. stercoralis relies upon sensory cues to aid in environmental navigation and coordinate developmental progression. Odorants, tastants, gases, and temperature have been shown to shape parasite behaviors that drive host seeking and infectivity; however, many of these sensory behaviors remain poorly understood, and their underlying molecular and neural mechanisms are largely uncharacterized. Disruption of sensory circuits essential to parasitism presents a promising strategy for future interventions. In this review, we describe our current understanding of sensory behaviors - namely olfactory, gustatory, gas sensing, and thermosensory behaviors - in Strongyloides spp. We also highlight the ever-growing cache of genetic tools optimized for use in Strongyloides that have facilitated these findings, including transgenesis, CRISPR/Cas9-mediated mutagenesis, RNAi, chemogenetic neuronal silencing, and the use of fluorescent biosensors to measure neuronal activity. Bolstered by these tools, we are poised to enter an era of rapid discovery in Strongyloides sensory neurobiology, which has the potential to shape pioneering advances in the prevention and treatment of strongyloidiasis.

摘要

经常被忽视的人体寄生虫粪类圆线虫感染了大约全球人口的 8%,给边缘化社区带来了不成比例的医疗和经济负担。虽然目前的化疗可以治疗粪类圆线虫病,但疾病复发和驱虫剂耐药的潜在威胁需要新的策略来控制线虫。在其生命周期中,粪类圆线虫依赖于感觉线索来帮助环境导航和协调发育进展。气味、味觉、气体和温度已被证明可以塑造寄生虫的行为,从而驱动宿主寻找和感染性;然而,许多这些感觉行为仍然知之甚少,其潜在的分子和神经机制在很大程度上尚未得到描述。破坏寄生虫生存所必需的感觉回路是未来干预的一个很有前途的策略。在这篇综述中,我们描述了我们目前对粪类圆线虫的感觉行为(即嗅觉、味觉、气体感应和热敏行为)的理解。我们还强调了不断增长的遗传工具库,这些工具优化用于粪类圆线虫,促进了这些发现,包括转基因、CRISPR/Cas9 介导的突变、RNAi、化学遗传神经元沉默以及使用荧光生物传感器测量神经元活动。有了这些工具,我们正准备进入粪类圆线虫感觉神经生物学的快速发现时代,这有可能为预防和治疗粪类圆线虫病带来开创性的进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4f2/9339661/5410ac7024d8/gr1.jpg

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