TropIQ Health Sciences, Nijmegen, the Netherlands.
University of Camerino, Camerino, Italy.
PLoS Biol. 2021 Dec 20;19(12):e3001426. doi: 10.1371/journal.pbio.3001426. eCollection 2021 Dec.
This work addresses the need for new chemical matter in product development for control of pest insects and vector-borne diseases. We present a barcoding strategy that enables phenotypic screens of blood-feeding insects against small molecules in microtiter plate-based arrays and apply this to discovery of novel systemic insecticides and compounds that block malaria parasite development in the mosquito vector. Encoding of the blood meals was achieved through recombinant DNA-tagged Asaia bacteria that successfully colonised Aedes and Anopheles mosquitoes. An arrayed screen of a collection of pesticides showed that chemical classes of avermectins, phenylpyrazoles, and neonicotinoids were enriched for compounds with systemic adulticide activity against Anopheles. Using a luminescent Plasmodium falciparum reporter strain, barcoded screens identified 48 drug-like transmission-blocking compounds from a 400-compound antimicrobial library. The approach significantly increases the throughput in phenotypic screening campaigns using adult insects and identifies novel candidate small molecules for disease control.
这项工作满足了在产品开发中控制害虫和病媒传播疾病方面对新化学物质的需求。我们提出了一种条形码策略，使血食昆虫对微滴定板基阵列中的小分子进行表型筛选，并将其应用于发现新型系统性杀虫剂和化合物，这些杀虫剂和化合物可阻断疟原虫在蚊子媒介中的发育。通过成功定殖于伊蚊和按蚊的重组 DNA 标记的 Asaia 细菌实现了血液餐的编码。对杀虫剂集合的阵列筛选表明，阿维菌素、苯并吡唑和新烟碱类等化学类别的化合物富含对按蚊具有系统性杀成虫活性的化合物。利用发光的恶性疟原虫报告株，条形码筛选从 400 种化合物的抗菌文库中鉴定出 48 种具有药物样传播阻断活性的化合物。该方法显著提高了使用成虫进行表型筛选的通量，并鉴定出用于疾病控制的新型候选小分子。
