Specialized Metabolites Reveal Evolutionary History and Geographic Dispersion of a Multilateral Symbiosis

Autor(es)

Fukuda, Taise T. H. ^{[1, 2]} ; Helfrich, Eric J. N. ^{[2, 3, 4]} ; Meyers, Emily ^{[2, 5]} ; Melo, Weilan G. P. ^[1] ; Van Arnam, Ethan B. ^{[2, 6, 7]} ; Andes, David R. ^[8] ; Currie, Cameron R. ^[9] ; Pupo, Monica T. ^[1] ; Clardy, Jon ^[2]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, BR-14040903 Ribeirao Preto, SP - Brazil

^[2] Harvard Med Sch, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 - USA

^[3] Goethe Univ Frankfurt, Inst Mol Bio Sci, D-60438 Frankfurt - Germany

^[4] LOEWE Ctr Translat Biodivers Genom TBG, D-60325 Frankfurt - Germany

^[5] Virginia Tech, Dept Chem, Blacksburg, VA 24061 - USA

^[6] Pitzer Coll, Keck Sci Dept, Claremont McKenna, Claremont, CA 91711 - USA

^[7] Scripps Coll, Keck Sci Dept, Claremont McKenna, Claremont, CA 91711 - USA

^[8] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Madison, WI 53705 - USA

^[9] Univ Wisconsin, Dept Bacteriol, Madison, WI 53706 - USA

• Tipo de documento: Artigo Científico
• Fonte: ACS CENTRAL SCIENCE; v. 7, n. 2, p. 292-299, FEB 24 2021.
• Citações Web of Science: 1

Resumo

Fungus-growing ants engage in a multilateral symbiosis: they cultivate a fungal garden as their primary food source and host symbiotic actinobacteria (Pseudonocardia spp.) that provide chemical defenses. The bacterial symbionts produce small specialized metabolites that protect the fungal garden from specific fungal pathogens (Escovopsis spp.), and in return, they are fed by the ant hosts. Multiple studies on the molecules underlying this symbiotic system have led to the discovery of a large number of structurally diverse antifungal molecules, but somewhat surprisingly no shared structural theme emerged from these studies. A large systematic study of Brazilian nests led to the discovery of the widespread production of a potent but overlooked antifungal agent, which we named attinimicin, by nearly two-thirds of all Pseudonocardia strains from multiple sites in Brazil. Here we report the structure of attinimicin, its putative biosynthetic gene cluster, and the evolutionary relationship between attinimicin and two related peptides, oxachelin A and cahuitamycin A. All three nonribosomal peptides are structural isomers with different primary peptide sequences. Attinimicin shows iron-dependent antifungal activity against specific environmental fungal parasites but no activity against the fungal cultivar. Attinimicin showed potent in vivo activity in a mouse Candida albicans infection model comparable to clinically used azole-containing antifungals. In situ detection of attinimicin in both ant nests and on worker ants supports an ecological role for attinimicin in protecting the fungal cultivar from pathogens. The geographic spread of the attinimicin biosynthetic gene cluster in Brazilian Pseudonocardia spp. marks attinimicin as the first specialized metabolite from ant-associated bacteria with broad geographic distribution. (AU)

• Processo FAPESP: 17/17305-0 - Estudo da simbiose bacteriana no sistema Cecropia-Azteca por meio de ferramentas químicas e genéticas
• Beneficiário: Taise Tomie Hebihara Fukuda
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado Direto
• Processo FAPESP: 15/26349-5 - Estudo químico e ecológico de microrganismos associados à simbiose Cecropia-Azteca
• Beneficiário: Taise Tomie Hebihara Fukuda
• 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