Department of Molecular Microbiology and Immunology, Malaria Research Institute, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
Global Health Medicines R&D, GSK, Tres Cantos, 28760 Madrid, Spain.
Science. 2023 Aug 4;381(6657):533-540. doi: 10.1126/science.adf8141. Epub 2023 Aug 3.
Malaria control demands the development of a wide range of complementary strategies. We describe the properties of a naturally occurring, non-genetically modified symbiotic bacterium, TC1, which was isolated from mosquitoes incapable of sustaining the development of parasites. TC1 inhibits early stages of development and subsequent transmission by the mosquito through secretion of a small-molecule inhibitor. We have identified this inhibitor to be the hydrophobic molecule harmane. We also found that, on mosquito contact, harmane penetrates the cuticle, inhibiting development. TC1 stably populates the mosquito gut, does not impose a fitness cost on the mosquito, and inhibits development for the mosquito's life. Contained field studies in Burkina Faso and modeling showed that TC1 has the potential to complement mosquito-targeted malaria transmission control.
疟疾控制需要开发广泛的互补策略。我们描述了一种从无法维持寄生虫发育的蚊子中分离出来的天然存在的非遗传修饰共生细菌 TC1 的特性。TC1 通过分泌小分子抑制剂来抑制寄生虫的早期发育和随后的蚊子传播。我们已经确定这种抑制剂是疏水分子哈尔曼。我们还发现，当接触蚊子时，哈尔曼穿透角质层，抑制发育。TC1 在蚊子肠道中稳定存在，不会对蚊子造成适应度成本，并且抑制蚊子的整个生命周期的发育。在布基纳法索进行的实地研究和建模表明，TC1 有可能补充针对蚊子的疟疾传播控制。
