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

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2020

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Ganley, Jack G.
Pandey, Ashmita
Sylvester, Kayla
Lu, Kuan-Yi
Toro-Moreno, Maria
Bradford, James M.
Champion, Cody J.
Xu, Jiannong

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Cell Chemical Biology. Cell Press. 2020, 27(7), pp. 817-826.e5. ISSN 2451-9456. eISSN 2451-9448. Available under: doi: 10.1016/j.chembiol.2020.06.004

Zusammenfassung

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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540 Chemie

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ISO 690GANLEY, Jack G., Ashmita PANDEY, Kayla SYLVESTER, Kuan-Yi LU, Maria TORO-MORENO, Sina RÜTSCHLIN, James M. BRADFORD, Cody J. CHAMPION, Thomas BÖTTCHER, Jiannong XU, Emily R. DERBYSHIRE, 2020. A Systematic Analysis of Mosquito-Microbiome Biosynthetic Gene Clusters Reveals Antimalarial Siderophores that Reduce Mosquito Reproduction Capacity. In: Cell Chemical Biology. Cell Press. 2020, 27(7), pp. 817-826.e5. ISSN 2451-9456. eISSN 2451-9448. Available under: doi: 10.1016/j.chembiol.2020.06.004
BibTex
@article{Ganley2020-07-16Syste-50832,
  year={2020},
  doi={10.1016/j.chembiol.2020.06.004},
  title={A Systematic Analysis of Mosquito-Microbiome Biosynthetic Gene Clusters Reveals Antimalarial Siderophores that Reduce Mosquito Reproduction Capacity},
  number={7},
  volume={27},
  issn={2451-9456},
  journal={Cell Chemical Biology},
  pages={817--826.e5},
  author={Ganley, Jack G. and Pandey, Ashmita and Sylvester, Kayla and Lu, Kuan-Yi and Toro-Moreno, Maria and Rütschlin, Sina and Bradford, James M. and Champion, Cody J. and Böttcher, Thomas and Xu, Jiannong and Derbyshire, Emily R.}
}
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