ApiAP2转录因子家族调控弓形虫生长发育的研究进展

doi:10.3864/j.issn.0578-1752.2024.13.015

中国农业科学 ›› 2024, Vol. 57 ›› Issue (13): 2687-2697.doi: 10.3864/j.issn.0578-1752.2024.13.015

ApiAP2转录因子家族调控弓形虫生长发育的研究进展

胡丹丹¹(), 罗润琪¹^,²(), 梁瑞英², 汪磊¹^,², 梁琳², 司红彬¹, 丁家波²(), 汤新明²()

¹ 广西大学动物科技学院，南宁 541000
² 中国农业科学院北京畜牧兽医研究所/农业农村部动物生物安全风险预警及防控重点实验室（北方）/农业农村部兽用生物制品与化学药品重点实验室，北京 100193

收稿日期:2023-12-23 接受日期:2024-03-14 出版日期:2024-07-09 发布日期:2024-07-09
通信作者:
丁家波，E-mail：dingjiabo@126.com。
汤新明，E-mail：tangxinming@caas.cn
联系方式: 胡丹丹，E-mail：hudandan@gxu.edu.cn。罗润琪，E-mail：luorunqi00@163.com。胡丹丹和罗润琪为同等贡献作者。
基金资助:
国家自然科学基金(32273035); 国家自然科学基金(31902295); 中国农业科学院青年创新专项(Y2023QC10)

Research Progress of ApiAP2 Transcription Factors in Regulating the Growth and Development of Toxoplasma gondii

HU DanDan¹(), LUO RunQi¹^,²(), LIANG RuiYing², WANG Lei¹^,², LIANG Lin², SI HongBin¹, DING JiaBo²(), TANG XinMing²()

¹ College of Animal Science and Technology, Guangxi University, Nanning 541000
² Institute of Animal Sciences, Chinese Academy of Agricultural Sciences/Key Laboratory of Animal Biosafety Risk Prevention and Control (North) of Ministry of Agriculture and Rural Affairs/Key Laboratory of Veterinary Biological Products and Chemical Drugs of Ministry of Agriculture and Rural Affairs, Beijing 100193

Received:2023-12-23 Accepted:2024-03-14 Published:2024-07-09 Online:2024-07-09

摘要/Abstract

摘要：

弓形虫病是世界范围内危害最为严重的人兽共患寄生虫病之一。WHO数据显示，全球人群弓形虫抗体阳性率在25%—50%。孕妇感染弓形虫引起的垂直传播严重危害胎儿及婴幼儿健康，弓形虫感染也是引起免疫缺陷病人死亡的主要因素。在畜牧生产中，弓形虫病引起孕畜流产、死胎，危害严重。弓形虫（Toxoplasma gondii）是一种专性细胞内原生动物寄生虫，属于顶复门原虫，生活史复杂，包括在中间宿主（人类和其他温血动物）的无性增殖和在终末宿主（猫科动物）的有性繁殖。为完成弓形虫在中间、终末宿主复杂的生命周期，其在不同发育阶段的转化及生长需要严格而精准的基因调控，因此揭示弓形虫生长发育的调控机制对治疗性药物和疫苗的研发具有重要意义。ApiAP2转录因子是一类具有AP2结构域和强大调节功能的蛋白家族，在疟原虫、弓形虫等寄生虫的生长发育中发挥核心调控作用，是阐明弓形虫不同生活史阶段发育与转化调控机制的突破口。弓形虫作为顶复门原虫研究的模式生物，有67个含AP2结构域的转录因子被注释，部分转录因子在弓形虫生命周期生长发育和转化过程中发挥核心调控功能，但尚有大部分AP2转录因子的生物学功能未知，尤其是针对有性繁殖阶段发育调控的研究较为匮乏。本文对已报道的弓形虫AP2转录因子的研究手段、生物学功能、调控的互作基因及网络进行系统梳理，旨在挖掘对弓形虫生长发育的重要节点起核心调控作用的基因或分子，在微观分子层面初步勾勒出弓形虫复杂生活史不同生长发育时期的调控机制，并对其在新型药物和疫苗研发中的作用及潜能进行展望。以期为动物弓形虫病的防控提供新的思路和切入点，阻断人弓形虫病的感染源，践行“人病兽防、关口前移”，实现“同一世界、同一健康”。

关键词: 刚地弓形虫, 生活史, 转录因子, 基因调控, 基因表达

Abstract:

Toxoplasmosis is one of the most serious zoonotic parasitic diseases in the world. WHO data show that the positive rate of Toxoplasma gondii antibody in the global population is 25%-50%. The vertical transmission caused by T. gondii infection in pregnant women seriously endangers the health of fetuses and infants, and T. gondii infection is also the main cause of death in immunocompromised patients. In livestock production, toxoplasmosis causes abortion and stillbirth in pregnant animals, which is seriously harmful. T. gondii is an obligate intracellular protozoan parasite that belongs to the apicomplexan protozoa, and its life cycle is complex, including asexual reproduction in intermediate hosts (humans and other warm-blooded animals) and sexual reproduction in terminal hosts (cats). In order to complete the complex life cycle of T. gondii in the intermediate and terminal hosts, its transformation and growth at different developmental stages require strict and accurate gene regulation. Therefore, revealing the regulatory mechanism of T. gondii growth and development is of great significance for the development of therapeutic drugs and vaccines. ApiAP2 transcription factor is a kind of protein family with AP2 domain and strong regulatory function, which plays a core regulatory role in the growth and development of parasites such as Plasmodium and T. gondii. It is a breakthrough to elucidate the regulation mechanism of development and transformation of T. gondii at different life cycle stages. As a model organism for the study of apicomplexan, 67 transcription factors containing AP2 domain have been annotated in T. gondii genome. Some of these transcription factors play crucial regulatory roles in the growth, development, and transformation processes of T. gondii throughout its life cycle. However, the biological functions of most AP2 transcription factors are unknown, especially the research on the development and regulation of sexual reproduction stage is relatively scarce. In this paper, the research methods, biological functions, regulatory interaction genes and networks of AP2 transcription factors of T. gondii have been systematically reviewed. The aim was to explore the genes or molecules that play a core regulatory role in the important nodes of T. gondii growth and development. The regulatory mechanism of different growth and development stages of T. gondii complex life cycle was preliminarily outlined at the micro molecular level, and its role and potential in the development of new drugs and vaccines were prospected. To provide new ideas and entry points for the prevention and control of animal toxoplasmosis and block the source of human toxoplasmosis infection, we should practice the concept of “disease prevention in animals and front-line defense” and strive to achieve “one world, one health” for everyone’s well-being.

Key words: Toxoplasma gondii, life cycle, transcription factors, gene regulation, gene expression

胡丹丹, 罗润琪, 梁瑞英, 汪磊, 梁琳, 司红彬, 丁家波, 汤新明. ApiAP2转录因子家族调控弓形虫生长发育的研究进展[J]. 中国农业科学, 2024, 57(13): 2687-2697.

HU DanDan, LUO RunQi, LIANG RuiYing, WANG Lei, LIANG Lin, SI HongBin, DING JiaBo, TANG XinMing. Research Progress of ApiAP2 Transcription Factors in Regulating the Growth and Development of Toxoplasma gondii[J]. Scientia Agricultura Sinica, 2024, 57(13): 2687-2697.

图/表 2

图1

表1

ApiAP2转录因子在弓形虫性生长发育中的调控作用"

名称 Name	基因号 GeneID	研究时期 Research period	作用 Function	文献来源 Reference
AP2IX-4	TGME49_288950	速殖子到缓殖子 Tachyzoite to bradyzoite	调控缓殖子分化和包囊形成；调控毒力相关基因表达 Regulate bradyzoite differentiation and cyst formation; regulation of virulence-related gene expression	[60]
AP2XI-4	TGME49_115760	速殖子到缓殖子 Tachyzoite to bradyzoite	调控缓殖子分化和包囊形成 Regulate bradyzoite differentiation and cyst formation	[62]
AP2IV-4	TGME49_318470	速殖子到缓殖子 Tachyzoite to bradyzoite	调控缓殖子分化和包囊形成 Regulate bradyzoite differentiation and cyst formation	[61]
AP2X-4	TGME49_224050	速殖子 Tachyzoite	调控棒状体分泌蛋白相关基因的表达；调控入侵，毒力和速殖子分裂 Regulate the expression of rhoptry secretory protein-related genes; regulate invasion, virulence and tachyzoite division	[42]
AP2XII-5	TGME49_24773	缓殖子 Bradyzoite	调控毒力相关基因表达 Regulation of virulence-related gene expression	[42]
AP2IX-5	TGME49_289710	速殖子 Tachyzoite	激活顶质体的分裂程序以促进速殖子分裂 Activate the division program of apicoplast to promote tachyzoite division	[56]
AP2X-5	TGME49_237090	速殖子S期/M期 Tachyzoite S/M	调控毒力相关基因表达 Regulation of virulence-related gene expression	[55]
AP2XI-5	TGME49_216220	速殖子 Tachyzoite	与 GCTAGC 基序结合 Bind to the GCTAGC motif	[54]
AP2IX-9	TGME49_306620	速殖子到缓殖子 Tachyzoite to bradyzoite	抑制缓殖子分化和包囊形成；适应性实验室进化的关键驱动因素 Inhibition of bradyzoite differentiation and cyst formation; The key driving factors of adaptive laboratory evolution	[41]
AP2IV-3	TGME49_318610	速殖子到缓殖子 Tachyzoite to bradyzoite	调控缓殖子分化和包囊形成 Regulate bradyzoite differentiation and cyst formation	[41]
AP2XII-2	TGME49_217700	速殖子到缓殖子 Tachyzoite to bradyzoite	调控速殖子分裂，抑制包囊形成；与HDAC3 / MORC复合物互作，抑制有性生殖启动 Regulate tachyzoite division and inhibit cyst formation; it interacts with HDAC3 / MORC complex to inhibit the initiation of sexual reproduction	[52,63]
AP2XII-1	TGME49_218960	速殖子到裂殖子 Tachyzoite to merozoite	调控速殖子分裂，抑制裂殖子形成; 抑制缓殖子以及包囊的形成；与HDAC3 / MORC复合物互作，可能抑制有性生殖启动 Regulate bradyzoite differentiation and cyst formation; Inhibiting the formation of bradyzoites and cysts in type II strains; Interaction with HDAC3 / MORC complex may inhibit initiation of sexual reproduction	[65]
AP2XI-2	TGME49_310900	速殖子到裂殖子 Tachyzoite to merozoite	调控入侵和毒力与HDAC3 / MORC复合物互作调控缓殖子分化和包囊形成；抑制裂殖子分化 Regulate bradyzoite differentiation and cyst formation; Interaction with HDAC3 / MORC complex may inhibit initiation of sexual reproduction; Regulate bradyzoite differentiation and cyst formation; Inhibition of merozoite differentiation	[64,66]
AP2IX-1	TGME49_267460	速殖子到裂殖子 Tachyzoite to merozoite	调控有性生殖阶段表面抗原表达 Regulation of surface antigen expression in sexual reproduction stage	[58]

表1

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ApiAP2转录因子家族调控弓形虫生长发育的研究进展

Research Progress of ApiAP2 Transcription Factors in Regulating the Growth and Development of Toxoplasma gondii

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