Selection for insecticide resistance can promote Plasmodium falciparum infection in Anopheles.

Selection for insecticide resistance can promote Plasmodium falciparum infection in Anopheles.
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杀虫剂抗性的选择可促进恶性疟原虫在按蚊体内的感染。

DOI:
10.1371/journal.ppat.1011448
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发表时间:
2023-06
期刊:
影响因子:
6.7
通讯作者:
--
中科院分区:
医学1区
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由于在病媒控制策略中广泛使用杀虫剂,按蚊对杀虫剂的抗性面临很强的选择压力。抗性机制可能会引起深刻影响蚊子生理的变化,然而人们对杀虫剂施加的选择性压力如何改变蚊子宿主和传播疟原虫感染的能力仍然知之甚少。从具有拟除虫菊酯抗性的田间冈比亚按蚊中,我们通过选择或丧失杀虫剂抗性,建立了抗性(RES)和敏感(SUS)菌落。我们发现,与感染恶性疟原虫的SUS雌性相比,RES中卵囊强度和生长速度增加,孢子子患病率和强度也增加。RES雌性感染强度的增加与kdrL1014F突变的存在无关,也不受细胞色素p450抑制的影响。脂质转运体脂蛋白(Lp)在RES中与SUS相比上调,至少部分与恶性疟原虫强度增加有关,但与杀虫剂抗性表型没有直接关系。有趣的是,我们观察到,尽管暴露于氯菊酯的RES雌性雌性恶性疟原虫感染不受影响,但暴露后这些雌性脂肪体中的脂质丰度降低,这表明脂质动员可能在应对杀虫剂攻击造成的损害中起作用。选择杀虫剂抗性可以增加恶性疟原虫的感染强度和生长速度,这一发现加强了评估蚊子在重复杀虫剂攻击过程中所经历的选择压力对疟疾传播动态的总体影响的必要性。杀虫剂耐药性对疟疾控制构成严重威胁。对拟除虫菊酯类杀虫剂(大多数驱虫蚊帐的有效成分)的抗药性现在在撒哈拉以南非洲广泛存在,从而降低了这些关键工具的效力。尽管对杀虫剂抗性机制进行了大量研究,但这些特性如何影响传播疟疾的按蚊的恶性疟原虫感染仍不清楚。我们建立了来自相同遗传背景的冈比亚按蚊(Anopheles gambiae s.l.)对拟除虫菊酯产生抗性和敏感的种群,并对恶性疟原虫进行了实验感染。我们发现,与易感人群相比,拟除虫菊酯耐药人群更支持疟疾寄生虫。这种效应不是由众所周知的杀虫剂抗性机制引起的,而是与脂质转运蛋白脂蛋白有关,脂质转运蛋白可能在抗性中起间接作用。
Insecticide resistance is under strong selective pressure in Anopheles mosquitoes due to widespread usage of insecticides in vector control strategies. Resistance mechanisms likely cause changes that profoundly affect mosquito physiology, yet it remains poorly understood how selective pressures imposed by insecticides may alter the ability of the mosquito to host and transmit a Plasmodium infection. From pyrethroid-resistant field-derived Anopheles gambiae s.l. mosquitoes, we established resistant (RES) and susceptible (SUS) colonies by either selection for, or loss of insecticide resistance. We show increased oocyst intensity and growth rate as well as increased sporozoite prevalence and intensity in RES compared to SUS females infected with Plasmodium falciparum. The increase in infection intensity in RES females was not associated with the presence of the kdrL1014F mutation and was not impacted by inhibition of Cytochrome P450s. The lipid transporter lipophorin (Lp), which was upregulated in RES compared to SUS, was at least partly implicated in the increased intensity of P. falciparum but not directly involved in the insecticide resistance phenotype. Interestingly, we observed that although P. falciparum infections were not affected when RES females were exposed to permethrin, these females had decreased lipid abundance in the fat body following exposure, pointing to a possible role for lipid mobilization in response to damage caused by insecticide challenge. The finding that selection for insecticide resistance can increase P. falciparum infection intensities and growth rate reinforces the need to assess the overall impact on malaria transmission dynamics caused by selective pressures mosquitoes experience during repeated insecticide challenge. Insecticide resistance poses a severe threat for malaria control. Resistance to pyrethroid insecticides, the active component of most insecticide-treated nets, is now widespread in sub-Saharan Africa, reducing the efficacy of these crucial tools. Despite significant research characterizing insecticide resistance mechanisms, it remains unknown how these traits influence Plasmodium falciparum infections in malaria-transmitting Anopheles mosquitoes. We established a pyrethroid-resistant and pyrethroid-susceptible population of Anopheles gambiae s.l. derived from the same genetic background and performed experimental infections with P. falciparum. We found that the pyrethroid-resistant population was more supportive of malaria parasites compared to the susceptible population. This effect was not caused by well-known insecticide resistance mechanisms, but linked with a lipid transporter, lipophorin, which may play an indirect role in resistance.
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