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.
Chevrette MG, Carlson CM, Ortega HE, Thomas C, Ananiev GE, Barns KJ, Book AJ, Cagnazzo J, Carlos C, Flanigan W, Grubbs KJ, Horn HA, Hoffmann FM, Klassen JL, Knack JJ, Lewin GR, McDonald BR, Muller L, Melo WGP, Pinto-Tomás AA, Schmitz A, Wendt-Pienkowski E, Wildman S, Zhao M, Zhang F, Bugni TS, Andes DR, Pupo MT, Currie CR. The antimicrobial potential of Streptomyces from insect microbiomes. Nat Commun. 2019 Jan 31;10(1):516. doi: 10.1038/s41467-019-08438-0. PubMed PMID: 30705269; PubMed Central PMCID: PMC6355912.
Keywords: antimicrobial potential, Streptomyces, insect microbiomes, genomics, multidrug resistant fungal pathogens, cyphomycin, metabolomics, antimicrobials.
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