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Nat Commun. 2019 Jan 31;10(1):516. doi: 10.1038/s41467-019-08438-0.

The antimicrobial potential of Streptomyces from insect microbiomes.

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Laboratory of Genetics, University of Wisconsin-Madison, Madison, 53706, WI, USA.
Department of Bacteriology, University of Wisconsin-Madison, Madison, 53706, WI, USA.
School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, 14040-903, SP, Brazil.
Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin-Madison, Madison, 53705, WI, USA.
McArdle Laboratory for Cancer Research, Wisconsin Institute for Medical Research, University of Wisconsin-Madison, Madison, 53705, WI, USA.
Department of Molecular and Cell Biology, University of Connecticut, Storrs, 06269, CT, USA.
Department of Biology, Large Lakes Observatory, University of Minnesota-Duluth, Duluth, 55812, MN, USA.
School of Biological Sciences, Georgia Institute of Technology, Atlanta, 30332, GA, USA.
Center for Research in Microscopic Structures and Department of Biochemistry, School of Medicine, University of Costa Rica, San José, 10102, Costa Rica.
Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, 53705, WI, USA.
Department of Bacteriology, University of Wisconsin-Madison, Madison, 53706, WI, USA.


Antimicrobial resistance is a global health crisis and few novel antimicrobials have been discovered in recent decades. Natural products, particularly from Streptomyces, are the source of most antimicrobials, yet discovery campaigns focusing on Streptomyces from the soil largely rediscover known compounds. Investigation of understudied and symbiotic sources has seen some success, yet no studies have systematically explored microbiomes for antimicrobials. Here we assess the distinct evolutionary lineages of Streptomyces from insect microbiomes as a source of new antimicrobials through large-scale isolations, bioactivity assays, genomics, metabolomics, and in vivo infection models. Insect-associated Streptomyces inhibit antimicrobial-resistant pathogens more than soil Streptomyces. Genomics and metabolomics reveal their diverse biosynthetic capabilities. Further, we describe cyphomycin, a new molecule active against multidrug resistant fungal pathogens. The evolutionary trajectories of Streptomyces from the insect microbiome influence their biosynthetic potential and ability to inhibit resistant pathogens, supporting the promise of this source in augmenting future antimicrobial discovery.

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