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

Discovery of MRSA active antibiotics using primary sequence from the human microbiome.
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DOI:
10.1038/nchembio.2207
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发表时间:
2016-12
影响因子:
14.8
通讯作者:
Brady SF
Brady SF
中科院分区:
生物学1区
文献类型:
--
作者:
Chu J;Vila-Farres X;Inoyama D;Ternei M;Cohen LJ;Gordon EA;Reddy BV;Charlop-Powers Z;Zebroski HA;Gallardo-Macias R;Jaskowski M;Satish S;Park S;Perlin DS;Freundlich JS;Brady SF

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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 applied 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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