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

Ganley, J. G.; Pandey, A.; Sylvester, K.; Lu, K.-Y.; Toro Moreno, M.; Rutschlin, S.; Bradford, J. M.; Champion, C. J.; Bottcher, T.; Xu, J.; Derbyshire, E. R.

doi:10.1101/2020.04.09.034280

bioRxiv · 10.1101/2020.04.09.034280

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

Ganley, J. G.·Pandey, A.·Sylvester, K.·Lu, K.-Y.·Toro Moreno, M.·Rutschlin, S.·Bradford, J. M.·Champion, C. J.·Bottcher, T.·Xu, J.·Derbyshire, E. R.

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Abstract

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.

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Ganley, J. G., Pandey, A., Sylvester, K., Lu, K.-Y., Toro Moreno, M., Rutschlin, S., Bradford, J. M., Champion, C. J., Bottcher, T., Xu, J., Derbyshire, E. R.. 2020-04-11. A Systematic Analysis of Mosquito-Microbiome Biosynthetic Gene Clusters Reveals Antimalarial Siderophores that Reduce Mosquito Reproduction Capacity. https://doi.org/10.1101/2020.04.09.034280

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