The mechanisms underlying the production of natural mosquito repellents by human beings

人类生产天然驱蚊剂的机制

• 批准号: MR/P021972/1
• 负责人: James Logan
• 金额: $ 85.56万
• 依托单位: London School of Hygiene & Tropical Medicine
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FP021972%2F1
• 关键词: mechanisms; underlying; production; natural; mosquito

Some human beings are bitten more than others by mosquitoes. From an evolutionary perspective this is fundamentally important since those that get bitten less often are less likely to die from lethal mosquito-borne diseases like malaria. Thus there is likely to be a selective advantage for being less attractive to malaria mosquitoes. Whether or not this is due to natural selection in humans, or because mosquitoes are simply avoiding unsuitable hosts is unknown, but our previous studies show that human differential attractiveness to mosquitoes is due to the natural production of key repellent chemicals given off by individuals who rarely get bitten. Essentially this could be thought of as the first line of defence related to the immune system. In a recent pilot study we showed that for Europeans how attractive you are to mosquitoes is controlled by your genes. We intend to extend this line of research and carry out a similar study amongst an indigenous African population that has traditionally been under intense selective pressure from malaria. Here we would anticipate finding genes for new repellent molecules that are under selection. The natural repellent chemicals that we have identified from our study of Europeans are effective repellents when applied to the skin, but what remains unknown is how the body produces these chemicals and which genes control this process. Preliminary studies show that some of the repellents can be produced by skin cells and there are likely candidate genes as potential targets. In this study we aim to compare identical and non-identical twins using chemical ecology and molecular genetic techniques to identify how the chemicals are produced and which genes are involved in production and regulation. This will give an understanding of how the body provides an important component of natural resistance to mosquitoes and provide a new potential treatment which stimulates production of these repellent chemicals in susceptible human beings. This could allow us to develop a more persistent application and eventually an oral treatment in the form of a pill which enhances the production of natural repellents to protect against mosquito bites, minimising the need for repeated skin-applied volatile repellents. This research has the potential to find new mosquito repellents that could be produced systemically, and elucidate one of the least understood innate immunity mechanisms: how we use chemical warfare to hide from vectors.

有些人比其他人更容易被蚊子叮咬。从进化的角度来看，这一点至关重要，因为那些被叮咬次数较少的人死于疟疾等致命的蚊媒疾病的可能性较小。因此，对疟疾蚊子吸引力较小可能存在选择性优势。这是否是由于人类的自然选择，或者因为蚊子只是为了避开不合适的宿主尚不清楚，但我们之前的研究表明，人类对蚊子的不同吸引力是由于很少被叮咬的个体自然产生的关键驱虫化学物质所致。本质上，这可以被认为是与免疫系统相关的第一道防线。在最近的一项试点研究中，我们表明，对于欧洲人来说，你对蚊子的吸引力是由你的基因控制的。我们打算扩展这一研究领域，并在传统上承受着疟疾强烈选择压力的非洲土著人群中开展类似的研究。在这里，我们预计会找到正在选择的新驱虫分子的基因。我们从对欧洲人的研究中发现，天然驱虫化学物质在应用于皮肤时是有效的驱虫剂，但仍然未知的是身体如何产生这些化学物质以及哪些基因控制这一过程。初步研究表明，一些驱虫剂可以由皮肤细胞产生，并且可能有候选基因作为潜在目标。在这项研究中，我们的目标是使用化学生态学和分子遗传学技术来比较同卵双胞胎和异卵双胞胎，以确定化学物质是如何产生的以及哪些基因参与产生和调节。这将有助于了解人体如何提供对蚊子的天然抵抗力的重要组成部分，并提供一种新的潜在治疗方法，刺激易感人群产生这些驱虫化学物质。这可以让我们开发出更持久的应用，并最终以药丸的形式进行口服治疗，从而提高天然驱虫剂的产量，以防止蚊虫叮咬，从而最大限度地减少重复皮肤涂抹挥发性驱虫剂的需要。这项研究有可能找到可以系统生产的新型驱蚊剂，并阐明人们最不了解的先天免疫机制之一：我们如何使用化学战来躲避媒介。

项目成果

Differential attraction in mosquito-human interactions and implications for disease control.

• DOI: 10.1098/rstb.2019.0811
• 发表时间: 2021-02-15
• 期刊: Philosophical transactions of the Royal Society of London. Series B, Biological sciences
• 作者: Martinez J;Showering A;Oke C;Jones RT;Logan JG
• 通讯作者: Logan JG

Additional file 1 of Skin microbiome alters attractiveness to Anopheles mosquitoes

皮肤微生物组的附加文件 1 改变对按蚊的吸引力

• DOI: 10.6084/m9.figshare.19582144
• 发表时间: 2022
• 作者: Showering A

Skin microbiome alters attractiveness to Anopheles mosquitoes.

皮肤微生物组改变了蚊子的吸引力。

• DOI: 10.1186/s12866-022-02502-4
• 发表时间: 2022-04-11
• 期刊: BMC microbiology
• 影响因子: 4.2