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Novel therapeutic agents from the bacterial symbionts of Brazilian invertebrates

Grant number: 13/50954-0
Support type:BIOTA-FAPESP Program - Thematic Grants
Duration: July 01, 2014 - June 30, 2019
Field of knowledge:Biological Sciences - Microbiology
Cooperation agreement: John E. Fogarty International Center (FIC/NIH)
Principal Investigator:Mônica Tallarico Pupo
Grantee:Mônica Tallarico Pupo
Principal investigator abroad: Jon Clardy
Institution abroad: Harvard University, Cambridge, United States
Home Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto, SP, Brazil
Co-Principal Investigators:Adriano Defini Andricopulo
Associated grant(s):16/50492-5 - Metabolic processes in the cooperative microbial symbionts of Brazilian membracids, AP.R
Associated scholarship(s):18/17502-2 - Natural products involved in the symbiosis between Amycolatopsis and attine ants, BP.MS
18/03650-0 - Analysis of steroids produced by symbiotic fungi isolated from the stingless bees' rearing cell, BP.MS
18/19128-0 - Isolation, preservation and cultivation of microbial strains associated with social insects, BP.TT
+ associated scholarships 18/03747-3 - Analysis of natural products involved in the interactions between Pseudonocardia and Escovopsis associated with Trachymyrmex ants using molecular networking, BP.MS
17/01188-4 - Relationship of the protozoan Crithidia spp with bacterioma associated with the stingless bee Melipona scutellaris: chemical, ecological and pharmacological studies, BP.PD
16/15872-1 - Identification of natural antiparasitic products produced by insect–bacterial symbiosis, BP.PD
15/16415-0 - Metabolic potential of fungus-garden microbiomes of Attini ants, BP.MS
15/04901-8 - Natural products from microorganisms associated with stingless bees: chemical, ecological and pharmacological studies, BP.DD
15/01001-6 - Discovering bacterial symbionts diversity associated with ants in different Brazilian biomes, BP.PD
15/01272-0 - Microbial strains: preservation, cultivation, extracts preparation, antibiotic screening and chemical profiling of extracts, BP.TT
14/14095-6 - Bacterial symbionts isolated from fungus-growing ants collected in remaining hotspots of biodiversity in São Paulo State as sources of antiparasitic compounds, BP.DD - associated scholarships

Abstract

An International Cooperative Biodiversity Group (ICBG) with an interdisciplinary leadership team of physicians, pharmacologists, evolutionary biologists, and chemists will discover and develop therapeutic agents produced by Brazilian symbiotic bacteria. The team will target three therapeutic areas: 1) infectious fungal pathogens, 2) Chagas disease and leishmaniasis, and 3), cancers of the blood-all three of which represent major threats to human health that need to be addressed with new therapeutic agents. This ICBG has focused screening platforms for all three diseases that will perform all the required steps from primary screens through in vivo mouse model studies. The ICBG will focus on identifying useful natural products from bacterial symbionts of social insects in Brazil, such as fungus-growing ants. Fungus-growing ants have specialized bacterial symbionts that provide chemical defenses against pathogenic fungi that threaten their communities. The ecological role of the bacterially produced chemical defenses - killing pathogenic fungi but sparing the fungal gardens and the ' insect host - matches the therapeutic requirements for antifungal, anticancer, and antiprotozoal agents. Our discovery efforts will make extensive use of cutting-edge technology and genomic approaches. Bacteria will be micro-cultured for high-throughput primary phenotypic screens, and priority strains will be re-cultured for secondary screens and dereplication. All bacterial strains will be genotyped (16S), and strains advancing along pipelines will have their genomes sequenced and subjected to bioinformatic analysis. In addition, the ICBG will undertake major efforts to catalog Brazil's microbial diversity, train Brazilian scientists, and support the development of drug discovery in the country. (AU)

Articles published in Agência FAPESP about the research grant
Bacteria and fungi play key roles in social insect colonies  
Bactérias e fungos desempenham papéis-chave nas colônias de insetos sociais 

Scientific publications (10)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
BRUNETTI, ANDRES E.; LYRA, MARIANA L.; MELO, WEILAN G. P.; ANDRADE, LAURA E.; PALACIOS-RODRIGUEZ, PABLO; PRADO, BARBARA M.; HADDAD, CELIO F. B.; PUPO, MONICA T.; LOPES, NORBERTO P. Symbiotic skin bacteria as a source for sex-specific scents in frogs. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v. 116, n. 6, p. 2124-2129, FEB 5 2019. Web of Science Citations: 0.
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, F. MICHAEL; KLASSEN, JONATHAN L.; KNACK, JENNIFER J.; LEWIN, GINA R.; MCDONALD, BRADON R.; MULLER, LAURA; MELO, WEILAN G. P.; PINTO-TOMAS, ADRIAN A.; SCHMITZ, AMBER; WENDT-PIENKOWSKI, EVELYN; WILDMAN, SCOTT; ZHAO, MIAO; ZHANG, FAN; BUGNI, TIM S.; ANDES, DAVID R.; PUPO, MONICA T.; CURRIE, CAMERON R. The antimicrobial potential of Streptomyces from insect microbiomes. NATURE COMMUNICATIONS, v. 10, JAN 31 2019. Web of Science Citations: 0.
MENEGATTI, CARLA; DA PAIXAO MELO, WEILAN GOMES; CARRAO, DANIEL BLASCKE; MORAES DE OLIVEIRA, ANDERSON RODRIGO; DO NASCIMENTO, FABIO SANTOS; LOPES, NORBERTO PEPORINE; PUPO, MONICA TALLARICO. Paenibacillus polymyxa Associated with the Stingless Bee Melipona scutellaris Produces Antimicrobial Compounds against Entomopathogens. Journal of Chemical Ecology, v. 44, n. 12, p. 1158-1169, DEC 2018. Web of Science Citations: 0.
LI, HONGJIE; SOSA-CALVO, JEFFREY; HORN, HEIDI A.; PUPO, MONICA T.; CLARDY, JON; RABELING, CHRISTIAN; SCHULTZ, TED R.; CURRIE, CAMERON R. Convergent evolution of complex structures for ant-bacterial defensive symbiosis in fungus-farming ants. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v. 115, n. 42, p. 10720-10725, OCT 16 2018. Web of Science Citations: 0.
CHAGAS, FERNANDA OLIVEIRA; PESSOTTI, RITA DE CASSIA; CARABALLO-RODRIGUEZ, ANDRES MAURICIO; PUPO, MONICA TALLARICO. Chemical signaling involved in plant-microbe interactions. CHEMICAL SOCIETY REVIEWS, v. 47, n. 5, p. 1652-1704, MAR 7 2018. Web of Science Citations: 6.
SILVA-JUNIOR, EDUARDO A.; RUZZINI, ANTONIO C.; PALUDO, CAMILA R.; NASCIMENTO, FABIO S.; CURRIE, CAMERON R.; CLARDY, JON; PUPO, MONICA T. Pyrazines from bacteria and ants: convergent chemistry within an ecological niche. SCIENTIFIC REPORTS, v. 8, FEB 7 2018. Web of Science Citations: 6.
PALUDO, CAMILA R.; MENEZES, CRISTIANO; SILVA-JUNIOR, EDUARDO A.; VOLLET-NETO, AYRTON; ANDRADE-DOMINGUEZ, ANDRES; PISHCHANY, GLEB; KHADEMPOUR, LILY; DO NASCIMENTO, FABIO S.; CURRIE, CAMERON R.; KOLTER, ROBERTO; CLARDY, JON; PUPO, MONICA T. Stingless Bee Larvae Require Fungal Steroid to Pupate. SCIENTIFIC REPORTS, v. 8, JAN 18 2018. Web of Science Citations: 3.
ORTEGA, HUMBERTO E.; BATISTA, JR., JOAO M.; MELO, WEILAN G. P.; CLARDY, JON; PUPO, MONICA T. Absolute configurations of griseorhodins A and C. Tetrahedron Letters, v. 58, n. 50, p. 4721-4723, DEC 13 2017. Web of Science Citations: 2.
DA SILVA-JUNIOR, EDUARDO AFONSO; PALUDO, CAMILA RAQUEL; VALADARES, LOHAN; LOPES, NORBERTO PEPORINE; DO NASCIMENTO, FABIO SANTOS; PUPO, MONICA TALLARICO. Aflatoxins produced by Aspergillus nomius ASR3, a pathogen isolated from the leaf-cutter ant Atta sexdens rubropilosa. REVISTA BRASILEIRA DE FARMACOGNOSIA-BRAZILIAN JOURNAL OF PHARMACOGNOSY, v. 27, n. 4, p. 529-532, JUL-AUG 2017. Web of Science Citations: 0.
PUPO, MONICA T.; CURRIE, CAMERON R.; CLARDY, JON. Microbial Symbionts of Insects are the Focus of the First International Cooperative Biodiversity Group (ICBG) in Brazil. Journal of the Brazilian Chemical Society, v. 28, n. 3, SI, p. 393-401, MAR 2017. Web of Science Citations: 1.

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