A Systematic Analysis of Mosquito-Microbiome Biosynthetic Gene Clusters Reveals Antimalarial Siderophores that Reduce Mosquito Reproduction Capacity
| Autor: | Sina Rütschlin, Ashmita Pandey, Emily R. Derbyshire, Jack G. Ganley, Kayla Sylvester, Jiannong Xu, Thomas Böttcher, Cody Champion, James M. Bradford, Maria Toro Moreno, Kuan-Yi Lu |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Plasmodium
Siderophore Anopheles gambiae Clinical Biochemistry Siderophores Bacterial genome size Biochemistry 01 natural sciences Antimalarials 03 medical and health sciences Metabolomics Phenols Anopheles parasitic diseases Drug Discovery Animals Humans Microbiome Molecular Biology Gene Phylogeny 030304 developmental biology Pharmacology Genetics Life Cycle Stages 0303 health sciences Bacteria biology 010405 organic chemistry Microbiota Reproduction biology.organism_classification 3. Good health 0104 chemical sciences Intestines Thiazoles Infectious disease (medical specialty) Multigene Family Molecular Medicine Genome Bacterial |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|