The antimicrobial potential of Streptomyces from insect microbiomes

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Chevrette, Marc G. ^{[1, 2]} ; Carlson, Caitlin M. ^[1] ; Ortega, Humberto E. ^[3] ; Thomas, Chris ^[4] ; Ananiev, Gene E. ^[5] ; Barns, Kenneth J. ^[4] ; Book, Adam J. ^[1] ; Cagnazzo, Julian ^[1] ; Carlos, Camila ^[1] ; Flanigan, Will ^[1] ; Grubbs, Kirk J. ^[1] ; Horn, Heidi A. ^[1] ; Hoffmann, F. Michael ^[5] ; Klassen, Jonathan L. ^[6] ; Knack, Jennifer J. ^[7] ; Lewin, Gina R. ^[8] ; McDonald, Bradon R. ^[1] ; Muller, Laura ^[1] ; Melo, Weilan G. P. ^[3] ; Pinto-Tomas, Adrian A. ^{[9, 10]} ; Schmitz, Amber ^[1] ; Wendt-Pienkowski, Evelyn ^[1] ; Wildman, Scott ^[4] ; Zhao, Miao ^[11] ; Zhang, Fan ^[4] ; Bugni, Tim S. ^[4] ; Andes, David R. ^[11] ; Pupo, Monica T. ^[3] ; Currie, Cameron R. ^[1]

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^[1] Univ Wisconsin, Dept Bacteriol, Madison, WI 53706 - USA

^[2] Univ Wisconsin, Genet Lab, Madison, WI 53706 - USA

^[3] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, BR-14040903 Ribeirao Preto, SP - Brazil

^[4] Univ Wisconsin, Sch Pharm, Pharmaceut Sci Div, Madison, WI 53705 - USA

^[5] Univ Wisconsin, Wisconsin Inst Med Res, McArdle Lab Canc Res, Madison, WI 53705 - USA

^[6] Univ Connecticut, Dept Mol & Cell Biol, Storrs, CT 06269 - USA

^[7] Univ Minnesota, Dept Biol, Large Lakes Observ, Duluth, MN 55812 - USA

^[8] Georgia Inst Technol, Sch Biol Sci, Atlanta, GA 30332 - USA

^[9] Univ Costa Rica, Sch Med, Ctr Res Microscop Struct, San Jose 10102 - Costa Rica

^[10] Univ Costa Rica, Sch Med, Dept Biochem, San Jose 10102 - Costa Rica

^[11] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Madison, WI 53705 - USA

• Tipo de documento: Artigo Científico
• Fonte: NATURE COMMUNICATIONS; v. 10, JAN 31 2019.
• Citações Web of Science: 16

Resumo

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. (AU)

• Processo FAPESP: 14/14095-6 - Bactérias simbiontes isoladas de formigas agricultoras coletadas em hotspots remanescentes de biodiversidade no estado de São Paulo como fontes de compostos antiparasitários
• Beneficiário: Humberto Enrique Ortega Dominguez
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 15/01001-6 - Descobrindo a diversidade simbionte bacteriana associada com formigas agricultoras em diferentes biomas brasileiros
• Beneficiário: Weilan Gomes da Paixão Melo
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 13/50954-0 - Novos agentes terapêuticos obtidos de bactérias simbiontes de invertebrados brasileiros
• Beneficiário: Mônica Tallarico Pupo
• Modalidade de apoio: Auxílio à Pesquisa - Programa BIOTA - Temático