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Discovery of MRSA active antibiotics using primary sequence from the human microbiome.
Chu, John; Vila-Farres, Xavier; Inoyama, Daigo; Ternei, Melinda; Cohen, Louis J; Gordon, Emma A; Reddy, Boojala Vijay B; Charlop-Powers, Zachary; Zebroski, Henry A; Gallardo-Macias, Ricardo; Jaskowski, Mark; Satish, Shruthi; Park, Steven; Perlin, David S; Freundlich, Joel S; Brady, Sean F.
Afiliação
  • Chu J; Laboratory of Genetically Encoded Small Molecules, The Rockefeller University, New York, New York, USA.
  • Vila-Farres X; Laboratory of Genetically Encoded Small Molecules, The Rockefeller University, New York, New York, USA.
  • Inoyama D; Department of Pharmacology, Physiology, and Neuroscience, Rutgers University-New Jersey Medical School, Newark, New Jersey, USA.
  • Ternei M; Laboratory of Genetically Encoded Small Molecules, The Rockefeller University, New York, New York, USA.
  • Cohen LJ; Laboratory of Genetically Encoded Small Molecules, The Rockefeller University, New York, New York, USA.
  • Gordon EA; Laboratory of Genetically Encoded Small Molecules, The Rockefeller University, New York, New York, USA.
  • Reddy BV; Laboratory of Genetically Encoded Small Molecules, The Rockefeller University, New York, New York, USA.
  • Charlop-Powers Z; Laboratory of Genetically Encoded Small Molecules, The Rockefeller University, New York, New York, USA.
  • Zebroski HA; Proteomics Resource Center, The Rockefeller University, New York, New York, USA.
  • Gallardo-Macias R; Department of Pharmacology, Physiology, and Neuroscience, Rutgers University-New Jersey Medical School, Newark, New Jersey, USA.
  • Jaskowski M; Department of Pharmacology, Physiology, and Neuroscience, Rutgers University-New Jersey Medical School, Newark, New Jersey, USA.
  • Satish S; Department of Pharmacology, Physiology, and Neuroscience, Rutgers University-New Jersey Medical School, Newark, New Jersey, USA.
  • Park S; Public Health Research Institute, Rutgers University-New Jersey Medical School, Newark, New Jersey, USA.
  • Perlin DS; Public Health Research Institute, Rutgers University-New Jersey Medical School, Newark, New Jersey, USA.
  • Freundlich JS; Department of Pharmacology, Physiology, and Neuroscience, Rutgers University-New Jersey Medical School, Newark, New Jersey, USA.
  • Brady SF; Laboratory of Genetically Encoded Small Molecules, The Rockefeller University, New York, New York, USA.
Nat Chem Biol ; 12(12): 1004-1006, 2016 Dec.
Article em En | MEDLINE | ID: mdl-27748750
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 ß-lactam activity against methicillin-resistant Staphylococcus aureus in mice, potentially providing a new treatment regimen.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Produtos Biológicos / Staphylococcus aureus Resistente à Meticilina / Descoberta de Drogas / Microbiota / Antibacterianos Limite: Humans Idioma: En Ano de publicação: 2016 Tipo de documento: Article
Texto completo
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XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Produtos Biológicos / Staphylococcus aureus Resistente à Meticilina / Descoberta de Drogas / Microbiota / Antibacterianos Limite: Humans Idioma: En Ano de publicação: 2016 Tipo de documento: Article