疟疾防控新策略：利用按蚊肠道共生菌阻断疟原虫传播

doi:10.12140/j.issn.1000-7423.2022.02.002

中国寄生虫学与寄生虫病杂志 ›› 2022, Vol. 40 ›› Issue (2): 140-145.doi: 10.12140/j.issn.1000-7423.2022.02.002

疟疾防控新策略：利用按蚊肠道共生菌阻断疟原虫传播

蒋永茂(), 高涵, 王四宝^*()

中国科学院昆虫发育与进化生物学重点实验室,中国科学院分子植物科学卓越创新中心,中国科学院上海植物生理生态研究所,上海 200032

收稿日期:2021-12-27 修回日期:2022-02-21 出版日期:2022-03-31 发布日期:2022-03-31
通讯作者: 王四宝
作者简介:蒋永茂（1994-）,男,博士研究生,从事蚊虫与疟原虫互作机制及防控新策略的研究。E-mail： ymjiang2016@cemps.ac.cn
基金资助:
国家自然科学基金(31830086);国家自然科学基金(32021001)

New strategies for malaria control: using mosquito symbiotic bacteria to block malaria transmission

JIANG Yong-mao(), GAO Han, WANG Si-bao^*()

CAS Key Laboratory of Insect Developmental and Evolutionary Biology, CAS Center for Excellence in Molecular Plant Sciences, Shanghai Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai 200032, China

Received:2021-12-27 Revised:2022-02-21 Online:2022-03-31 Published:2022-03-31
Contact: WANG Si-bao
Supported by:
National Natural Science Foundation of China(31830086);National Natural Science Foundation of China(32021001)

摘要/Abstract

摘要：

疟疾是一种由疟原虫感染引发的蚊媒传染病。由于缺乏高效的疫苗,目前疟疾防控主要依靠控制蚊虫的杀虫剂以及抗疟药物。然而,杀虫剂的滥用导致蚊虫产生抗药性、以及耐抗疟药物疟原虫株的出现和扩散,使疟疾防控面临严峻挑战。近年来疟疾防控进展缓慢,亟需发展新的防控策略和工具。利用肠道共生菌阻断疟原虫传播的技术是一种新型的源头防控策略,该策略近年来取得显著的进展。本文对该技术的发展及研究现状进行综述,并对应用该技术面临的挑战进行探讨。

关键词: 疟疾, 按蚊, 疟原虫, 共生菌, 共生菌阻断技术

Abstract:

Malaria is a mosquito borne parasitic disease caused by Plasmodium infection. In the absence of highly effective vaccines, controlling malaria mainly relies on mosquito-controlling insecticides and antimalarial drugs. However, increased resistance to insecticides among mosquitoes and the emergence and spread of antimalarial drug-resistant parasites have become significant challenges in the fight against malaria. In recent years, global progress toward malaria prevention and control has remained stagnant, and new strategies to control malaria are urgently needed. Symbiotic control is a new strategy that uses mosquito gut symbiotic microorganisms to control vector mosquitoes or reduce vector competence. This strategy has made remarkable progress in recent years. Here, the advances in the development and research of this technology are reviewed, and the challenges in the application of symbiotic control of malaria are discussed.

Key words: Malaria, Anopheles, Plasmodium, Symbiotic bacteria, Symbiotic control

中图分类号:

R531.3

蒋永茂, 高涵, 王四宝. 疟疾防控新策略：利用按蚊肠道共生菌阻断疟原虫传播[J]. 中国寄生虫学与寄生虫病杂志, 2022, 40(2): 140-145.

JIANG Yong-mao, GAO Han, WANG Si-bao. New strategies for malaria control: using mosquito symbiotic bacteria to block malaria transmission[J]. Chinese Journal of Parasitology and Parasitic Diseases, 2022, 40(2): 140-145.

图/表 4

图1

图2

表1

表2

转基因共生菌阻断疟原虫传播研究进展

底盘菌及表达的抗疟效应因子	针对的疟原虫种类	效果	备注	参考文献
大肠埃希菌（E. coli）表达的Pbs21scFv-Shiva1	伯氏疟原虫	受感染的蚊虫数量和卵囊密度显著降低	这是一种减毒的实验室细菌,在蚊的肠道中存活率很低;重组效应分子附着在细菌表面影响效果	[20]
大肠埃希菌（E. coli）表达的SM1和mPLA2	伯氏疟原虫	显著抑制伯氏疟原虫对按蚊中肠的感染	非共生菌;重组效应分子形成包涵体,影响阻断效果;吸血后96 h蚊体内无法检测到	[32]
绿僵菌（Metarhizium anisopliae）表达的[SM1]₈、PfNPNA-1、 Scorpine	恶性疟原虫	显著抑制疟原虫传播,对子孢子阶段抑制率分别为71%、85%、90%	杀蚊真菌	[25]
成团泛菌（Pantoea agglomerans）表达多种效应分子如[(SM1)₂]、mPLA2、pbs21scFv-Shiva1、Scorpine、Pro:EPIP（EPIP）₄	恶性疟原虫、伯氏疟原虫	① 利用大肠埃希菌HlyA系统分泌多种抗疟原虫效应蛋白 ② 对恶性疟原虫和伯氏疟原虫抑制率高达98% ③ 转基因共生菌对自身和按蚊的生长发育无影响	Pantoea具有一定的共生能力,不具有水平或垂直传播能力	[21]
沙雷氏菌属新菌株AS1（Serratia）表达的（MP2）₂-scorpine-（EPIP）₄-Shiva1-（SM2）₂	恶性疟原虫	① 首次发现了能在按蚊中代代相传的肠道共生细菌 ② 成功构建了抗疟效应分子的高效分泌表达系统,能显著抑制疟原虫感染 ③ 攻克了驱动抗疟原虫基因快速散播到整个蚊群的关键难题	AS1具有优异的定植和跨代传播能力,可快速散播到整个蚊群	[14]
Asaia通过血液诱导型启动子条件性表达的scorpine	伯氏疟原虫	① 较好地抑制疟原虫感染 ② 与组成性表达相比,条件性表达表现出更好的适应度	通过诱导型启动子促进肠道菌的适应性	[37]

表2

参考文献 37

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效应分子	靶向疟原虫类型	靶向阶段	作用机制	参考文献
毒杀疟原虫
Scorpine	恶性疟原虫、伯氏疟原虫	配子体-动合子	裂解疟原虫	[14,21,25]
Shiva1	恶性疟原虫、伯氏疟原虫	同上	裂解疟原虫	[14,21,26]
Shiva3	恶性疟原虫、伯氏疟原虫	同上	裂解疟原虫	[27]
CecB	恶性疟原虫	卵囊	裂解疟原虫	[28]
Gambicin	恶性疟原虫、伯氏疟原虫	动合子	裂解疟原虫	[29]
靶向结合疟原虫
EPIP	恶性疟原虫、伯氏疟原虫	动合子	抑制血纤维蛋白溶酶原与动合子结合,阻止疟原虫侵入按蚊中肠	[14,30]
Pro: EPIP	恶性疟原虫、伯氏疟原虫	动合子	阻断动合子穿越中肠围食膜,并防止血纤维蛋白溶酶原与动合子结合	[21]
Pbs21scFv-Shiva1	恶性疟原虫、伯氏疟原虫	配子体-卵囊	一种单链单克隆抗体（scFv）,以动合子表面主要蛋白Pbs21为靶点,并与裂解肽Shiva1结合发挥作用	[20,21]
PfNPNA-1	恶性疟原虫	子孢子	识别恶性疟原虫表面环孢子虫蛋白的重复区（Asn-Pro-Asn-Ala）	[25]
与蚊虫中肠或唾液腺上皮细胞相互作用
SM1/[SM1]₂/[SM1]₈	恶性疟原虫、伯氏疟原虫	动合子、子孢子	阻断动合子对中肠上皮细胞的侵袭和子孢子对唾液腺上皮细胞的侵袭	[21,25,31,32]
MP2	恶性疟原虫、伯氏疟原虫	动合子	阻断动合子对中肠上皮细胞的侵袭	[33,34]
mPLA2	恶性疟原虫、伯氏疟原虫	动合子	通过改变中肠上皮膜的特性,抑制动合子入侵中肠	[14,21,32,34]
Pro	恶性疟原虫、伯氏疟原虫	动合子	抑制几丁质酶和阻断动合子穿越中肠围食膜	[35]
Pchtscfv	恶性疟原虫	动合子	抑制几丁质酶和阻断动合子穿越中肠围食膜	[36]

疟疾防控新策略：利用按蚊肠道共生菌阻断疟原虫传播

New strategies for malaria control: using mosquito symbiotic bacteria to block malaria transmission

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