identifier	taxonID	type	CVterm	format	language	title	description	additionalInformationURL	UsageTerms	rights	Owner	contributor	creator	bibliographicCitation
03F98792895CFFE0FF85C480FD03FD38.text	03F98792895CFFE0FF85C480FD03FD38.taxon	http://purl.org/dc/dcmitype/Text	http://rs.tdwg.org/ontology/voc/SPMInfoItems#GeneralDescription	text/html	en	Streptomyces	<div><p>Streptomyces</p> <p>Marc G. Chevrette 1,2, Caitlin M. Carlson 2, Humberto E. Ortega 3, Chris Thomas 4, Gene E. Ananiev 5, Kenneth J. Barns 4, Adam J. Book 2, Julian Cagnazzo 2, Camila Carlos 2, Will Flanigan 2, Kirk J. Grubbs 2, Heidi A. Horn 2, F. Michael Hoffmann 5, Jonathan L. Klassen 6, Jennifer J. Knack 7, Gina R. Lewin 8, Bradon R. McDonald 2, Laura Muller 2, Weilan G.P. Melo 3, Adrián A. Pinto-Tomás 9, Amber Schmitz 2, Evelyn Wendt-Pienkowski 2, Scott Wildman 4, Miao Zhao 10, Fan Zhang 4, Tim S. Bugni 4, David R. Andes 10, Monica T. Pupo 3 &amp; Cameron R. Currie 2</p> <p>Antimicrobial resistance is a global health crisis and few novel antimicrobials have been</p> <p>discovered in recent decades. Natural products, particularly from Streptomyces, are the source</p> <p>of most antimicrobials, yet discovery campaigns focusing on Streptomyces from the soil</p> <p>largely rediscover known compounds. Investigation of understudied and symbiotic sources</p> <p>has seen some success, yet no studies have systematically explored microbiomes for anti-</p> <p>microbials. Here we assess the distinct evolutionary lineages of Streptomyces from insect</p> <p>microbiomes as a source of new antimicrobials through large-scale isolations, bioactivity</p> <p>assays, genomics, metabolomics, and in vivo infection models. Insect-associated Streptomyces</p> <p>inhibit antimicrobial-resistant pathogens more than soil Streptomyces. Genomics and meta-</p> <p>bolomics reveal their diverse biosynthetic capabilities. Further, we describe cyphomycin,</p> <p>a new molecule active against multidrug resistant fungal pathogens. The evolutionary</p> <p>trajectories of Streptomyces from the insect microbiome influence their biosynthetic potential</p> <p>and ability to inhibit resistant pathogens, supporting the promise of this source in augmenting</p> <p>future antimicrobial discovery.</p> <p>1 Laboratory of Genetics, University of Wisconsin-Madison, Madison 53706 WI, USA. 2 Department of Bacteriology, University of Wisconsin-Madison, Madison 53706 WI, USA. 3 School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14040-903 SP, Brazil. 4 Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin-Madison, Madison 53705 WI, USA. 5 McArdle Laboratory for Cancer Research, Wisconsin Institute for Medical Research, University of Wisconsin-Madison, Madison 53705 WI, USA. 6 Department of Molecular and Cell Biology, University of Connecticut, Storrs 0 6269 CT, USA. 7 Department of Biology, Large Lakes Observatory, University of Minnesota-Duluth, Duluth 55812 MN, USA. 8 School of Biological Sciences, Georgia Institute of Technology, Atlanta 30332 GA, USA. 9 Center for Research in Microscopic Structures and Department of Biochemistry, School of Medicine, University of Costa Rica, San José 10102, Costa Rica. 10 Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison 53705 WI, USA. Correspondence and requests for materials should be addressed to C.R.C. (email: currie@bact.wisc.edu)</p> <p>(2019) 10: 516 | https://doi.org/10.1038/s41467-019-08438-0 | www.nature.com/naturecommunications</p> <p>he rapid emergence of antimicrobial resistance in bacterial T and fungal pathogens is a public health crisis1,2. Novel therapeutics are needed to counter resistance, yet no new antimicrobial classes have been clinically approved in over three decades3. Natural products are the main source of antimicrobials, the majority of which are produced by Actinobacteria cultured from the soil3,4. However, contemporary studies of this once prolific source of novel chemistry face dramatically diminishing returns, largely due to the rediscovery of known compounds5. Efforts to address this issue, including genome mining6,7, synthetic biology8, and exploring alternative microbial sources, such as marine microbial environments9 – 12 and underrepresented taxa13,14, have yielded limited success. To combat the continual emergence of multidrug-resistant pathogens, there is a critical and constant need to discover new antimicrobial natural products.</p> <p>Natural products are the language of microbial interactions, evolved to mediate communication and antagonism among and between species15,16. Within microbiomes, the ecology and diversity of natural product chemistry reflect the underlying interactions between the microbial community, host, and environment. Exploration of the specialized natural product chemistry embedded within host microbiomes is an emerging new paradigm in antimicrobial drug discovery. Antimicrobials have recently been discovered from the microbiomes of diverse eukaryotic hosts, ranging from sea squirts17 to humans18. A particularly compelling source of novel antimicrobials lies in defensive symbioses, where bacterial symbionts produce antimicrobials to protect against opportunistic and specialized pathogens19 – 23. In insects, these symbioses are best exemplified in fungus-growing ant19 – 21, solitary digger wasp22, and southern pine beetle23 (Fig. 1a, right) systems, where Actinobacteria (typically Streptomyces) provide chemical defenses, paralleling our own reliance on the antimicrobials produced by these taxa to combat infectious disease. For example, the Streptomyces symbiotically associated with the southern pine beetle (Dendroctonus frontalis) produce the secondary metabolites frontalamide A, frontalamide B, and mycangimycin23,24. Mycangimycin inhibits the beetles ’ antagonistic fungus Ophiostoma minus and has potent inhibitory activity against malaria while the frontalamides have general antifungal activity23,24. Solitary wasps also associate with Streptomyces that provide antibacterial and antifungal chemical protection to their larvae through production of streptochlorin, a variety of piericidin analogs, and other molecules25. The antifungal compound sceliphrolactam was discovered from Streptomyces associated with a mud dauber wasp25. The natalamycin derivatives produced by Streptomyces from the fungus-growing termite system provide similar antifungal defense26. Further, over 10 new natural products with antimicrobial activity have been identified from the chemical characterization of approximately</p> <p>(2019) 10: 516 | https://doi.org/10.1038/s41467-019-08438-0 | www.nature.com/naturecommunications</p> <p>100 insect- Streptomyces strains23,24,27,28. Globally there are over five million insect species that occupy virtually every terrestrial niche29. Although insects are among the most diverse organisms on the planet29, studies of Actinobacteria from these systems have been limited to only a few insect orders, specifically Hymenoptera and Coleoptera. Further, insects themselves exhibit complex chemistry that mediates and maintains the diversity of their ecological interactions30.</p> <p>Here, we systematically examine our hypothesis that insect microbiomes are a valuable source of new antimicrobials. The extreme diversity of insects presents untapped potential for drug discovery from their equally diverse microbial communities. However, the breadth of natural product biosynthesis and antimicrobial potential within insect microbiomes remains relatively unknown. We hypothesize that Streptomyces from insect microbiomes represent a promising source of antimicrobials with distinct evolutionary histories from soil Streptomyces, upon which most antimicrobial discovery efforts have focused. We focus on Streptomyces because this genus: (i) is the source of most clinically used antibacterials and antifungals, (ii) has established genetic tools to facilitate development8, and (iii) has been implicated in readily forming associations with diverse insect hosts31.</p> </div>	https://treatment.plazi.org/id/03F98792895CFFE0FF85C480FD03FD38	Public Domain	No known copyright restrictions apply. See Agosti, D., Egloff, W., 2009. Taxonomic information exchange and copyright: the Plazi approach. BMC Research Notes 2009, 2:53 for further explanation.		Plazi	Chevrette, Marc G.;Carlson, Caitlin M.;Ortega, Humberto E.;Thomas, Chris;Ananiev, Gene E.;Barns, Kenneth J.;Book, Adam J.;Cagnazzo, Julian;Carlos, Camila;Flanigan, Will;Grubbs, Kirk J.;Horn, Heidi A.;Hoffmann, Michael;Klassen, Jonathan L.;Knack, Jennifer J.;Lewin, Gina R.;McDonald, Bradon R.;Mulle, Laura;Melo, Weilan G. P.;Pinto-Tomás, Adrián A.;Schmitz, Amber;Wendt-Pienkowski, Evelyn;Wildman, Scott;Zhao, Miao;Zhang, Fan;Bugni, Tim S.;Andes, David R.;Pupo, Monica T.;Currie, Cameron R.	Chevrette, Marc G., Carlson, Caitlin M., Ortega, Humberto E., Thomas, Chris, Ananiev, Gene E., Barns, Kenneth J., Book, Adam J., Cagnazzo, Julian, Carlos, Camila, Flanigan, Will, Grubbs, Kirk J., Horn, Heidi A., Hoffmann, Michael, Klassen, Jonathan L., Knack, Jennifer J., Lewin, Gina R., McDonald, Bradon R., Mulle, Laura, Melo, Weilan G. P., Pinto-Tomás, Adrián A., Schmitz, Amber, Wendt-Pienkowski, Evelyn, Wildman, Scott, Zhao, Miao, Zhang, Fan, Bugni, Tim S., Andes, David R., Pupo, Monica T., Currie, Cameron R. (2019): The antimicrobial potential from insect microbiomes of Streptomyces. Nature Communications 10 (516): 1-11, DOI: 10.1038/s41467-019-08438-0
03F987928955FFEBFC51C6D8FD28FB0B.text	03F987928955FFEBFC51C6D8FD28FB0B.taxon	http://purl.org/dc/dcmitype/Text	http://rs.tdwg.org/ontology/voc/SPMInfoItems#GeneralDescription	text/html	en	Data Walker 1862	<div><p>Data availability</p> <p>Genomic data can be found at DOI: 10.5281/zenodo.2436565. All other data are available in the main text or the supplementary materials; Permits for collections and accessing genetic resources in Brazil were issued by SISBIO #46555 – 5 and CNPq # 010936 /2014 – 9. Costa Rican collecting permits were issued by the Comisión Institucional de Biodiversidad (Institutional Biodiversity Committee, University of Costa Rica; Resolutions # 0 12 and 020; Material Transfer Agreement MTA VI-4307 – 2013) and authorized by La Selva Biological Station and Las Brisas Nature Reserve. A modified version of the southern pine beetle (Fig. 1) photo from Erich G. Vallery is used under the Creative Commons Attribution 3.0 License. Photos of Cyphomyrmex (Figs. 1 and 5) are used under a perpetual commercial license from Alexander Wild.</p> <p>Received: 18 October 2018 Accepted: 11 January 2019</p></div> 	https://treatment.plazi.org/id/03F987928955FFEBFC51C6D8FD28FB0B	Public Domain	No known copyright restrictions apply. See Agosti, D., Egloff, W., 2009. Taxonomic information exchange and copyright: the Plazi approach. BMC Research Notes 2009, 2:53 for further explanation.		Plazi	Chevrette, Marc G.;Carlson, Caitlin M.;Ortega, Humberto E.;Thomas, Chris;Ananiev, Gene E.;Barns, Kenneth J.;Book, Adam J.;Cagnazzo, Julian;Carlos, Camila;Flanigan, Will;Grubbs, Kirk J.;Horn, Heidi A.;Hoffmann, Michael;Klassen, Jonathan L.;Knack, Jennifer J.;Lewin, Gina R.;McDonald, Bradon R.;Mulle, Laura;Melo, Weilan G. P.;Pinto-Tomás, Adrián A.;Schmitz, Amber;Wendt-Pienkowski, Evelyn;Wildman, Scott;Zhao, Miao;Zhang, Fan;Bugni, Tim S.;Andes, David R.;Pupo, Monica T.;Currie, Cameron R.	Chevrette, Marc G., Carlson, Caitlin M., Ortega, Humberto E., Thomas, Chris, Ananiev, Gene E., Barns, Kenneth J., Book, Adam J., Cagnazzo, Julian, Carlos, Camila, Flanigan, Will, Grubbs, Kirk J., Horn, Heidi A., Hoffmann, Michael, Klassen, Jonathan L., Knack, Jennifer J., Lewin, Gina R., McDonald, Bradon R., Mulle, Laura, Melo, Weilan G. P., Pinto-Tomás, Adrián A., Schmitz, Amber, Wendt-Pienkowski, Evelyn, Wildman, Scott, Zhao, Miao, Zhang, Fan, Bugni, Tim S., Andes, David R., Pupo, Monica T., Currie, Cameron R. (2019): The antimicrobial potential from insect microbiomes of Streptomyces. Nature Communications 10 (516): 1-11, DOI: 10.1038/s41467-019-08438-0
