Discovery of MRSA active antibiotics using primary sequence from the human microbiome

John Chu; Xavier Vila-Farres; Daigo Inoyama; Melinda Ternei; Louis J. Cohen; Emma A. Gordon; Boojala Vijay B. Reddy; Zachary Charlop-Powers; Henry A. Zebroski; Ricardo Gallardo-Macias; Mark Jaskowski; Shruthi Satish; Steven Park; David S. Perlin; Joel S. Freundlich; Sean F. Brady

doi:10.1038/nchembio.2207

Discovery of MRSA active antibiotics using primary sequence from the human microbiome

John Chu, Xavier Vila-Farres, Daigo Inoyama, Melinda Ternei, Louis J. Cohen, Emma A. Gordon, Boojala Vijay B. Reddy, Zachary Charlop-Powers, Henry A. Zebroski, Ricardo Gallardo-Macias, Mark Jaskowski, Shruthi Satish, Steven Park, David S. Perlin, Joel S. Freundlich, Sean F. Brady

Research output: Contribution to journal › Article › peer-review

115 Scopus citations

Abstract

Here we present a natural product discovery approach, whereby structures are bioinformatically predicted from primary sequence and produced by chemical synthesis (synthetic-bioinformatic natural products, syn-BNPs), circumventing the need for bacterial culture and gene expression. When we applied the approach to nonribosomal peptide synthetase gene clusters from human-associated bacteria, we identified the humimycins. These antibiotics inhibit lipid II flippase and potentiate β-lactam activity against methicillin-resistant Staphylococcus aureus in mice, potentially providing a new treatment regimen.

Original language	English (US)
Pages (from-to)	1004-1006
Number of pages	3
Journal	Nature Chemical Biology
Volume	12
Issue number	12
DOIs	https://doi.org/10.1038/nchembio.2207
State	Published - Dec 1 2016
Externally published	Yes

Bibliographical note

Funding Information:
We thank members of the Fischetti (MRSA), Tomasz (MRSA) and Marraffini (S. aureus, S. delphini, S. intermedius, and S. pseudo-intermedius) laboratories at the Rockefeller University for providing strains. This work was supported by the Rainin Foundation, US National Institutes of Health grants U19AI109713 (D.S.P.) and F32 29 AI110029 (Z.C.-P.).

Publisher Copyright:
© 2016 Nature America, Inc., part of Springer Nature.

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10.1038/nchembio.2207

http://europepmc.org/articles/pmc5117632

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Chu, J., Vila-Farres, X., Inoyama, D., Ternei, M., Cohen, L. J., Gordon, E. A., Reddy, B. V. B., Charlop-Powers, Z., Zebroski, H. A., Gallardo-Macias, R., Jaskowski, M., Satish, S., Park, S., Perlin, D. S., Freundlich, J. S., & Brady, S. F. (2016). Discovery of MRSA active antibiotics using primary sequence from the human microbiome. Nature Chemical Biology, 12(12), 1004-1006. https://doi.org/10.1038/nchembio.2207

Chu, J, Vila-Farres, X, Inoyama, D, Ternei, M, Cohen, LJ, Gordon, EA, Reddy, BVB, Charlop-Powers, Z, Zebroski, HA, Gallardo-Macias, R, Jaskowski, M, Satish, S, Park, S, Perlin, DS, Freundlich, JS & Brady, SF 2016, 'Discovery of MRSA active antibiotics using primary sequence from the human microbiome', Nature Chemical Biology, vol. 12, no. 12, pp. 1004-1006. https://doi.org/10.1038/nchembio.2207

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Discovery of MRSA active antibiotics using primary sequence from the human microbiome

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