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

Abstract

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

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.

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Figures/Tables 2

Fig. 1

Table 1

Regulator functions of ApiAP2 transcription factors in Toxoplasma gondii life cycle"

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]

Table 1

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