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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 - September 30, 2020
Field of knowledge:Biological Sciences - Microbiology - Organic Chemistry
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 SPRINT
Associated scholarship(s):19/16559-3 - Biosynthetic studies of bioactive macrolactone polyketide from Streptomyces sp. ICBG311, BP.MS
19/19099-3 - Genomic analysis of antibiotic-producing Pseudonocardia associated with Attini ants, BP.TT
18/17502-2 - Natural products involved in the symbiosis between Amycolatopsis and attine ants., BP.MS
+ associated scholarships 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
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)

Matéria(s) publicada(s) na Agência FAPESP sobre o auxílio:
Stingless bee species depend on a complex fungal community to survive 
Compound that kills drug-resistant fungi is isolated from ant microbiota 
Bacteria and fungi play key roles in social insect colonies  
Bactérias e fungos desempenham papéis-chave nas colônias de insetos sociais 
Articles published in other media outlets (40 total):
More itemsLess items
Blog Beatriz Achával (Argentina): Las larvas de una especie de abejas sin aguijón dependen de una comunidad fúngica compleja para sobrevivir (13/Jul/2020)
Mundo Agropecuario (Venezuela): Las especies de abejas sin aguijón dependen de una comunidad fúngica compleja para sobrevivir (24/Oct/2019)
Phys.Org (Reino Unido): Stingless bee species depend on a complex fungal community to survive (23/Oct/2019)
Technology Networks (Reino Unido): Fungal Symbiosis Vital for Bee Development Threatened by Pesticides (23/Oct/2019)
SciTech Daily (EUA): Bizarre Species of Stingless Bees Depend on a Complex Fungal Community to Survive (23/Oct/2019)
Science Bulletin: Stingless bee species depend on a complex fungal community to survive (23/Oct/2019)
Alternative Learning: Bizarre Species of Stingless Bees Depend on a Complex Fungal Community to Survive (23/Oct/2019)
Focus Technica: Bizarre Species of Stingless Bees Depend on a Complex Fungal Community to Survive (23/Oct/2019)
TekCrispy (Nicarágua): Las larvas de abejas sin aguijón necesitan de tres hongos para alcanzar la adultez (23/Oct/2019)
Tech Deeps: Bizarre Species of Stingless Bees Depend on a Complex Fungal Community to Survive (23/Oct/2019)
The Bee Report: Bizarre Species of Stingless Bees Depend on a Complex Fungal Community to Survive (23/Oct/2019)
WebsFavourites.Com (Nigéria): Bizarre Species of Stingless Bees Depend on a Complex Fungal Community to Survive (23/Oct/2019)
Santech 360 (Índia): Stingless bee species depend on a complex fungal community to survive (23/Oct/2019)
Bioengineer (Reino Unido): Stingless bee species depend on a complex fungal community to survive (22/Oct/2019)
Science Codex: Stingless bee species depend on a complex fungal community to survive (22/Oct/2019)
LabRoots (EUA): Stingless bee species depend on a complex fungal community to survive (22/Oct/2019)
Scienmag Science Magazine (Reino Unido): Stingless Bee Species Depend On A Complex Fungal Community To Survive (22/Oct/2019)
Brightsurf: Stingless bee species depend on a complex fungal community to survive (22/Oct/2019)
Career Biotech: Stingless bee species depend on a complex fungal community to survive (22/Oct/2019)
Pharma Jobs: Stingless bee species depend on a complex fungal community to survive (22/Oct/2019)
Agenparl (Itália): Stingless bee species depend on a complex fungal community to survive (22/Oct/2019)
7thSpace: Stingless bee species depend on a complex fungal community to survive (22/Oct/2019)
Scienstack: Stingless bee species depend on a complex fungal community to survive (22/Oct/2019)
A Lavoura online: Agroquímicos podem afetar relação simbiótica da abelha canudo (08/Oct/2019)
Ciclo Vivo: Mais 57 agrotóxicos são liberados: 382 registros neste ano (04/Oct/2019)
Espaço Ecológico no Ar: Abelha canudo depende de complexa comunidade fúngica para sobreviver (03/Oct/2019)
Revista Ecológico online: Abelha canudo depende de complexa comunidade fúngica para sobreviver (03/Oct/2019)
Sou Ecológico: Abelha canudo depende de complexa comunidade fúngica para sobreviver (03/Oct/2019)
Confap - Conselho Nacional das Fundações Estaduais de Amparo à Pesquisa: Abelha canudo depende de complexa comunidade fúngica para sobreviver (02/Oct/2019)
Ecoa: Abelha canudo depende de complexa comunidade fúngica para sobreviver (02/Oct/2019)
Planet Earth Water Air Green Brazil: Abelha canudo depende de complexa comunidade fúngica para sobreviver (02/Oct/2019)
AlcidesFaria: Abelha canudo depende de complexa comunidade fúngica para sobreviver (02/Oct/2019)
Portal Gazeta de São Carlos: Abelha canudo depende de complexa comunidade fúngica para sobreviver (02/Oct/2019)
W Rádio Brasil: Abelha canudo depende de complexa comunidade fúngica para sobreviver (02/Oct/2019)
Scientific Inquirer (EUA): The next antibiotic may come from insect microbiota (19/Aug/2019)
Em Sintonia: Formiguinhas (26/Jun/2019)
Mother Nature: Compound that kills drug-resistant fungi is isolated from ant microbiota (05/May/2019)
Science and Technology Research News (EUA): Compound That Kills Drug-Resistant Fungi Is Isolated from Ant Microbiota (26/Apr/2019)
Technology Networks (Reino Unido): Ant Microbiota Compound Offers Problematic Fungi Killing Potential (12/Apr/2019)
Mindzilla (Reino Unido): Compound that Kills Drug-Resistant Fungi is Isolated from Ant Microbiota (05/Apr/2019)

Scientific publications (24)
(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)
BETANCUR, LUZ A.; FORERO, ABEL M.; VINCHIRA-VILLARRAGA, DIANA M.; CARDENAS, JUAN D.; ROMERO-OTERO, ADRIANA; CHAGAS, FERNANDA O.; PUPO, MONICA T.; CASTELLANOS, LEONARDO; RAMOS, FREDDY A. NMR-based metabolic profiling to follow the production of anti- phytopathogenic compounds in the culture of the marine strain Streptomyces sp. PNM-9. MICROBIOLOGICAL RESEARCH, v. 239, OCT 2020. Web of Science Citations: 0.
MENEGATTI, CARLA; FUKUDA, TAISE T. H.; PUPO, MONICA T. Chemical Ecology in Insect-microbe Interactions in the Neotropics. Planta Medica, AUG 2020. Web of Science Citations: 0.
BARCOTO, MARIANA O.; CARLOS-SHANLEY, CAMILA; FAN, HUAN; FERRO, MILENE; NAGAMOTO, NILSON S.; BACCI, JR., MAURICIO; CURRIE, CAMERON R.; RODRIGUES, ANDRE. Fungus-growing insects host a distinctive microbiota apparently adapted to the fungiculture environment. SCIENTIFIC REPORTS, v. 10, n. 1 JUL 24 2020. Web of Science Citations: 0.
RIES, LAURE N. A.; PARDESHI, LAKHANSING; DONG, ZHICLIANG; TAN, KAELING; STEENWYK, JACOB L.; COLABARDINI, ANA CRISTINA; FERREIRA FILHO, JAIRE A.; DE CASTRO, PATRICIA A.; SILVA, LILIAN P.; PREITE, NYCOLAS W.; ALMEIDA, FAUSTO; DE ASSIS, LEANDRO J.; DOS SANTOS, RENATO A. C.; BOWYER, PAUL; BROMLEY, MICHAEL; OWENS, REBECCA A.; DOYLE, SEAN; DEMASI, MARILENE; HERNANDEZ, DIEGO C. R.; NETTO, LUIS EDUARDO S.; PUPO, MONICA T.; ROKAS, ANTONIS; LOURES, V, FLAVIO; WONG, KOON H.; GOLDMAN, GUSTAVO H. The Aspergillus fumigatus transcription factor RglT is important for gliotoxin biosynthesis and self-protection, and virulence. PLOS PATHOGENS, v. 16, n. 7 JUL 2020. Web of Science Citations: 0.
BATISTA, JULIANA H.; LEAL, FERNANDA C.; FUKUDA, TAISE T. H.; ALCOFORADO DINIZ, JULIANA; ALMEIDA, FAUSTO; PUPO, MONICA T.; DA SILVA NETO, JOSE F. Interplay between two quorum sensing-regulated pathways, violacein biosynthesis and VacJ/Yrb, dictates outer membrane vesicle biogenesis in Chromobacterium violaceum. ENVIRONMENTAL MICROBIOLOGY, v. 22, n. 6 MAY 2020. Web of Science Citations: 0.
FUKUDA, TAISE T. H.; CASSILLY, CHELSI D.; GERDT, JOSEPH P.; HENKE, MATTHEW T.; HELFRICH, ERIC J. N.; MEVERS, EMILY. Research Tales from the Clardy Laboratory: Function-Driven Natural Product Discovery. Journal of Natural Products, v. 83, n. 3, SI, p. 744-755, MAR 27 2020. Web of Science Citations: 0.
MENEGATTI, CARLA; LOURENZON, VITOR BRUNO; RODRIGUEZ-HERNANDEZ, DIEGO; DA PAIXAO MELO, WEILAN GOMES; GOMES FERREIRA, LEONARDO LUIZ; ANDRICOPULO, ADRIANO DEFINI; DO NASCIMENTO, FABIO SANTOS; PUPO, MONICA TALLARICO. Meliponamycins: Antimicrobials from Stingless Bee-Associated Streptomyces sp.. Journal of Natural Products, v. 83, n. 3, SI, p. 610-616, MAR 27 2020. Web of Science Citations: 2.
ORTEGA, HUMBERTO E.; BATISTA, JR., JOAO M.; MELO, WEILAN G. P.; DE PAULA, GABRIELA T.; PUPO, MONICA T. Structure and Absolute Configuration of Secondary Metabolites from Two Strains of Streptomyces chartreusis Associated with Attine Ants. Journal of the Brazilian Chemical Society, v. 30, n. 12, SI, p. 2672-2680, DEC 2019. Web of Science Citations: 0.
ORTEGA, HUMBERTO E.; FERREIRA, LEONARDO L. G.; MELO, WEILAN G. P.; OLIVEIRA, ANA LIGIA L.; RAMOS ALVARENGA, RENE F.; LOPES, NORBERTO P.; BUGNI, TIM S.; ANDRICOPULO, ADRIANO D.; PUPO, MONICA T. Antifungal compounds from Streptomyces associated with attine ants also inhibit Leishmania donovani. PLoS Neglected Tropical Diseases, v. 13, n. 8 AUG 2019. Web of Science Citations: 0.
PALUDO, CAMILA RAQUEL; PISHCHANY, GLEB; ANDRADE-DOMINGUEZ, ANDRES; SILVA-JUNIOR, EDUARDO AFONSO; MENEZES, CRISTIANO; NASCIMENTO, FABIO SANTOS; CURRIE, CAMERON R.; KOLTER, ROBERTO; CLARDY, JON; PUPO, MONICA TALLARICO. Microbial community modulates growth of symbiotic fungus required for stingless bee metamorphosis. PLoS One, v. 14, n. 7 JUL 25 2019. Web of Science Citations: 0.
RODRIGUEZ-HERNANDEZ, DIEGO; MELO, WEILAN G. P.; MENEGATTI, CARLA; LOURENZON, VITOR B.; DO NASCIMENTO, FABIO S.; PUPO, MONICA T. Actinobacteria associated with stingless bees biosynthesize bioactive polyketides against bacterial pathogens. NEW JOURNAL OF CHEMISTRY, v. 43, n. 25, p. 10109-10117, JUL 7 2019. Web of Science Citations: 0.
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: 2.
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: 16.
HUMBERTO E. ORTEGA; JOÃO M. BATISTA JR.; WEILAN G. P. MELO; GABRIELA T. DE PAULA; MÔNICA T. PUPO. Structure and Absolute Configuration of Secondary Metabolites from Two Strains of Streptomyces chartreusis Associated with Attine Ants. Journal of the Brazilian Chemical Society, v. 30, n. 12, p. 2672-2680, Dez. 2019.
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: 3.
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: 10.
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: 21.
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: 11.
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: 10.
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: 4.
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: 4.
CHAGAS, FERNANDA O.; RUZZINI, ANTONIO C.; BACHA, V, LARISSA; SAMBORSKYY, MARKYIAN; CONTI, RAPHAEL; PESSOTTI, RITA C.; DE OLIVEIRA, LUCIANA G.; CLARDY, JON; PUPO, MONICA T. Genome Sequence of Streptomyces sp. Strain RTd22, an Endophyte of the Mexican Sunflower. MICROBIOLOGY RESOURCE ANNOUNCEMENTS, v. 4, n. 4 JUL-AUG 2016. Web of Science Citations: 0.
PALUDO, CAMILA R.; RUZZINI, EANTONIO C.; SILVA-JUNIOR, EDUARDO A.; PISHCHANY, GLEB; CURRIE, CAMERON R.; NASCIMENTO, FABIO S.; KOLTER, ROBERTO G.; CLARDY, JON; PUPO, MONICA T. Whole-Genome Sequence of Bacillus sp. SDLI1, Isolated from the Social Bee Scaptotrigona depilis. MICROBIOLOGY RESOURCE ANNOUNCEMENTS, v. 4, n. 2 MAR-APR 2016. Web of Science Citations: 2.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.