Advances in infectious disease control strategies through genetic manipulation of insect microbiomes have heightened interest in microbially produced small molecules within mosquitoes. Herein, 33 mosquito-associated bacterial genomes were mined and over 700 putative biosynthetic gene clusters (BGCs) were identified, 135 of which belong to known classes of BGCs. After an in-depth analysis of the 135 BGCs, iron-binding siderophores were chosen for further investigation due to their high abundance and well-characterized bioactivities. Through various metabolomic strategies, eight siderophore scaffolds were identified in six strains of mosquito-associated bacteria. Among these, serratiochelin A and pyochelin were found to reduce female Anopheles gambiae overall fecundity likely by lowering their blood-feeding rate. Serratiochelin A and pyochelin were further found to inhibit the Plasmodium parasite asexual blood and liver stages in vitro. Our work supplies a bioinformatic resource for future mosquito-microbiome studies and highlights an understudied source of bioactive small molecules.

通过对昆虫微生物组进行遗传控制来控制传染病的策略已引起人们对蚊子内微生物产生的小分子的关注。在这里，开采了33个与蚊子有关的细菌基因组，并鉴定了700多个假定的生物合成基因簇（BGC），其中135个属于已知的BGC类。经过对135个BGC的深入分析，由于铁结合铁的丰度高和生物活性良好，因此选择铁结合铁载体进行进一步研究。通过各种代谢组学策略，在六个与蚊子相关的细菌菌株中鉴定出八个铁载体。其中，serratiochelin A和pyochelin被发现可以减少雌性冈比亚按蚊降低繁殖力可能会降低整体繁殖力。进一步发现Serratiochelin A和Pyochelin在体外抑制疟原虫的无性血液和肝脏阶段。我们的工作为未来的蚊子微生物组研究提供了生物信息学资源，并着重介绍了生物活性小分子的未被充分研究的来源。