A Systematic Analysis of Mosquito-Microbiome Biosynthetic Gene Clusters Reveals Antimalarial Siderophores that Reduce Mosquito Reproduction Capacity.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Ganley, JG; Pandey, A; Sylvester, K; Lu, K-Y; Toro-Moreno, M; Rütschlin, S; Bradford, JM; Champion, CJ; Böttcher, T; Xu, J; Derbyshire, ER

Published Date

  • July 2, 2020

Published In

Volume / Issue

  • 27 / 7

Start / End Page

  • 817 - 826.e5

PubMed ID

  • 32619453

Electronic International Standard Serial Number (EISSN)

  • 2451-9448

International Standard Serial Number (ISSN)

  • 2451-9456

Digital Object Identifier (DOI)

  • 10.1016/j.chembiol.2020.06.004

Language

  • eng