Transmissibility of clinically relevant atovaquone-resistant Plasmodium falciparum by anopheline mosquitoes.
Transmissibility of clinically relevant atovaquone-resistant Plasmodium falciparum by anopheline mosquitoes.
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按蚊传播临床相关的阿托伐醌抗性恶性疟原虫。
DOI：
10.1101/2023.02.07.527535
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Owen,Andrew
中科院分区：
文献类型：
--
作者：
Balta,VictoriaA;Stiffler,Deborah;Sayeed,Abeer;Tripathi,AbhaiK;Elahi,Rubayet;Mlambo,Godfree;Bakshi,RahulP;Dziedzic,AmandaG;Jedlicka,AnneE;Nenortas,Elizabeth;Romero-Rodriguez,Keyla;Canonizado,MatthewA;Mann,Alexis;Owen,Andrew
疟疾病例和死亡人数不断上升，突出表明需要采取新的干预措施。长效注射药物，例如目前用于艾滋病毒预防的药物，提供了疟疾“化学疫苗”的前景，它结合了药物（如阿托伐酮）的效力和生物疫苗的持久性。然而，令人关注的是耐药寄生虫的可能选择和传播。我们通过产生临床相关的、高度耐阿托伐醌的、能够感染蚊子的恶性疟原虫突变体来解决这个问题。在东南亚（斯氏按蚊）或非洲（冈比亚按蚊）蚊子和人源化小鼠中平行评估了仅因细胞色素b单个Y268S突变而不同的等基因配对菌株。突变的适应度成本在整个生命周期中都很明显，在体外无性繁殖的寄生虫和蚊子体内寄生虫的逐渐丧失中都是如此。在许多独立的实验中，对数百只蚊子的唾液腺进行显微镜检查，甚至没有检测到一个Y268S孢子体，这一缺陷无法通过与野生型寄生虫共同感染来挽救。此外，尽管野生型寄生虫从安。携带人类肝细胞和红细胞的小鼠，用y268s喂养的蚊子多次尝试失败：通过显微镜、体外培养或PCR均未发现小鼠组织中存在寄生虫的证据。这些研究证实了临床上相关的阿托伐酮耐药恶性疟原虫在蚊子中的严重到致死的适应成本，并且它们显著降低了其在野外传播的可能性。
Rising numbers of malaria cases and deaths underscore the need for new interventions. Long-acting injectable medications, such as those now in use for HIV prophylaxis, offer the prospect of a malaria “chemical vaccine”, combining the efficacy of a drug (like atovaquone) with the durability of a biological vaccine. Of concern, however, is the possible selection and transmission of drug-resistant parasites. We addressed this question by generating clinically relevant, highly atovaquone-resistant, Plasmodium falciparum mutants competent to infect mosquitoes. Isogenic paired strains, that differ only by a single Y268S mutation in cytochrome b, were evaluated in parallel in southeast Asian (Anopheles stephensi) or African (Anopheles gambiae) mosquitoes, and thence in humanized mice. Fitness costs of the mutation were evident along the lifecycle, in asexual parasite growth in vitro and in a progressive loss of parasites in the mosquito. In numerous independent experiments, microscopic exam of salivary glands from hundreds of mosquitoes failed to detect even one Y268S sporozoite, a defect not rescued by coinfection with wild type parasites. Furthermore, despite uniformly successful transmission of wild type parasites from An. stephensi to FRG NOD huHep mice bearing human hepatocytes and erythrocytes, multiple attempts with Y268S-fed mosquitoes failed: there was no evidence of parasites in mouse tissues by microscopy, in vitro culture, or PCR. These studies confirm a severe-to-lethal fitness cost of clinically relevant atovaquone-resistant P. falciparum in the mosquito, and they significantly lessen the likelihood of their transmission in the field.
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DOI：
10.1111/j.1432-1033.1986.tb09854.x
发表时间：
1986-08-15
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
BUNGER, R;SOBOLL, S
通讯作者：
SOBOLL, S
使用空间局部 31P NMR 波谱研究正常犬心肌的透壁高能磷酸盐分布和对工作负荷变化的反应
影响因子：
3.3
作者：
P. Robitaille;H. Merkle;B. Lew;G. Path;K. Hendrich;P. Lindstrom;A. From;M. Garwood;R. Bache;K. Uğurbil
通讯作者：
K. Uğurbil
豚鼠心脏去甲肾上腺素输注过程中的磷酸化电位和腺苷释放。
DOI：
10.1152/ajpheart.1987.253.5.h1184
发表时间：
1987
期刊：
The American journal of physiology
影响因子：
--
作者：
He,MX;Wangler,RD;Dillon,PF;Romig,GD;Sparks,HV
通讯作者：
Sparks,HV
心脏中腺苷形成的不同部位。
影响因子：
--
作者：
W. Schutz;Jürgen Schrader;Eckehart Gerlach
通讯作者：
Eckehart Gerlach
大鼠心肌细胞腺苷转运和代谢。
影响因子：
--
作者：
D. Ford;M. Rovetto
通讯作者：
M. Rovetto