He Ran, Xu Luyang, Guo Maochuan, Cheng Kai, Song Ziyi, Xie Yue, Wang Hui, Zhou Xuan, Gu Xiaobin, Xu Jing, Deng Huidan, Yang Guangyou
Department of Parasitology, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China.
Microbiol Spectr. 2024 Oct 22;12(12):e0073724. doi: 10.1128/spectrum.00737-24.
Scabies is a contagious zoonotic parasitic disease that causes a substantial risk to both human and animal health and results in significant financial losses. No vaccine is available for scabies, and drug resistance to the conventional treatment for the disease has increased. Histone deacetylase (HDAC) modifies proteins by removing acetyl moieties from histones, regulates transcription, and is crucial for the immune system and apoptotic processes. This study aimed to clone, express, and determine the immunoreactivity of HDAC-2 and HDAC-3 of scabies mites to investigate their potential as scabies drug targets. The effects of inhibitors on recombinant HDAC-2 (rSsHDAC-2) and rSsHDAC-3, as well as on the survival rate and ultrastructure of scabies mites , were also verified. The findings showed that the inhibitors reduced the acetylase activity of rSsHDAC-2 and rSsHDAC-3. Additionally, these inhibitors could significantly reduce the survival rate of scabies mites, making structural alterations in the mites such as mitochondrial pyknosis and cytoplasmic vacuoles and reaching a fatality rate of 76.7% after 24 h of action. In conclusion, HDAC-2 and HDAC-3 were critical to the survival of scabies mites and might be targeted by medications. Furthermore, the effect of inhibitors on the survival rate and structure of isolated scabies mites provides a new direction for developing therapeutic drugs for scabies.IMPORTANCEIn this study, we successfully cloned and expressed recombinant SsHDAC-2 and SsHDAC-3 in a prokaryotic system and confirmed their acetylation-deacetylase activities. These results provide a solid experimental foundation for subsequent research on SsHDAC-2 and SsHDAC-3. Furthermore, we report for the first time the use of SsHDAC-2 and SsHDAC-3 as drug targets. We demonstrated that the inhibition of these HDACs by pharmacological agents can lead to structural damage in the parasite, thereby impacting the survival activity of the scabies mite. This finding opens up a novel therapeutic avenue for the treatment of scabies.
疥疮是一种具有传染性的人畜共患寄生虫病，对人类和动物健康都构成重大风险，并导致巨大的经济损失。目前尚无用于治疗疥疮的疫苗，而且该疾病对传统治疗方法的耐药性有所增加。组蛋白去乙酰化酶（HDAC）通过从组蛋白中去除乙酰基部分来修饰蛋白质，调节转录，并且对免疫系统和凋亡过程至关重要。本研究旨在克隆、表达并确定疥螨HDAC-2和HDAC-3的免疫反应性，以研究它们作为疥疮药物靶点的潜力。还验证了抑制剂对重组HDAC-2（rSsHDAC-2）和rSsHDAC-3以及对疥螨存活率和超微结构的影响。研究结果表明，这些抑制剂降低了rSsHDAC-2和rSsHDAC-3的乙酰化酶活性。此外，这些抑制剂可显著降低疥螨的存活率，使螨体出现线粒体固缩和细胞质空泡等结构改变，作用24小时后死亡率达到76.7%。总之，HDAC-2和HDAC-3对疥螨的存活至关重要，可能成为药物作用靶点。此外，抑制剂对分离的疥螨存活率和结构的影响为开发疥疮治疗药物提供了新方向。重要性在本研究中，我们成功地在原核系统中克隆并表达了重组SsHDAC-2和SsHDAC-3，并证实了它们的乙酰化-去乙酰化酶活性。这些结果为后续对SsHDAC-2和SsHDAC-3的研究提供了坚实的实验基础。此外，我们首次报道将SsHDAC-2和SsHDAC-3用作药物靶点。我们证明，通过药物抑制这些HDAC可导致寄生虫结构损伤，从而影响疥螨的生存活性。这一发现为疥疮的治疗开辟了一条新的治疗途径。
