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

Rutgers, The State University, Hackensack Meridian School of Medicine

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

75 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	American English
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

ASJC Scopus subject areas

Molecular Biology
Cell Biology

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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

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title = "Discovery of MRSA active antibiotics using primary sequence from the human microbiome",

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.",

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

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year = "2016",

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doi = "10.1038/nchembio.2207",

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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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AU - Chu, John

AU - Vila-Farres, Xavier

AU - Inoyama, Daigo

AU - Ternei, Melinda

AU - Cohen, Louis J.

AU - Gordon, Emma A.

AU - Reddy, Boojala Vijay B.

AU - Charlop-Powers, Zachary

AU - Zebroski, Henry A.

AU - Gallardo-Macias, Ricardo

AU - Jaskowski, Mark

AU - Satish, Shruthi

AU - Park, Steven

AU - Perlin, David S.

AU - Freundlich, Joel S.

AU - Brady, Sean F.

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AB - 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.

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SP - 1004

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JO - Nature Chemical Biology

JF - Nature Chemical Biology

IS - 12

ER -

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

Abstract

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