AP1 will discover therapeutic agents for Chagas, leishmaniasis and other diseases by accessing Brazil's microbial diversity. No effective treatment is available for Chagas disease, and treatment of leishmaniasis is still incomplete. Brazil is one of the world's megabiodiverse countries, incorporating 70% of the world's catalogued animal and plant species and some 15-20% of the world's biological diversity. In spite of this huge potential, not a single natural product isolated from Brazilian natural sources has been developed. Most natural products research in Brazil has prioritized plants; this ICBG will focus on the bacterial symbionts of social insects that have evolved to chemically defend their hosts. In addition to discovering new chemotypes from Brazil's microbial diversity, this proposal will expand the knowledge and appreciation of it and thereby contribute to informing biodiversity preservation policies in Brazil. Bacterial strains will be isolated from invertebrates collected in different Brazilian biomes, such as Cerrado, Atlantic Forest, Amazon and Caatinga, and preserved in AP1. Strains that showed desired potency and selectivity in AP4 primary assays will be evaluated in in vitro antiparasitic assays against Trypanosoma cruzi and Leishmania donovani in AP1. Antiparasitic extracts will be fractionated in AP1 using different chromatographic methods, and active natural products will have their structures established using spectroscopic and spectrometric data analyses. This AP1 will also aim the training of undergraduate students, graduate students and postdoctoral fellows in multi-investigator interdisciplinary research with a focus on natural products from bacterial symbionts. This sort of interdisciplinary research requires training both in specific subjects as well as a broad appreciation of therapeutic development. Training Brazilian students and young researchers through short and long term internships in the US associated laboratories will enable them to meet the expectations of the Brazilian government in facing country's major challenges for scientific and technological development.
| Van Arnam, Ethan B; Currie, Cameron R; Clardy, Jon (2018) Defense contracts: molecular protection in insect-microbe symbioses. Chem Soc Rev 47:1638-1651 |
| Silva-Junior, Eduardo A; Ruzzini, Antonio C; Paludo, Camila R et al. (2018) Pyrazines from bacteria and ants: convergent chemistry within an ecological niche. Sci Rep 8:2595 |
| Li, Hongjie; Sosa-Calvo, Jeffrey; Horn, Heidi A et al. (2018) Convergent evolution of complex structures for ant-bacterial defensive symbiosis in fungus-farming ants. Proc Natl Acad Sci U S A 115:10720-10725 |
| Paludo, Camila R; Menezes, Cristiano; Silva-Junior, Eduardo A et al. (2018) Stingless Bee Larvae Require Fungal Steroid to Pupate. Sci Rep 8:1122 |
| Ortega, Humberto E; Batista Jr, João M; Melo, Weilan G P et al. (2017) Absolute Configurations of Griseorhodins A and C. Tetrahedron Lett 58:4721-4723 |
| Ramadhar, Timothy R; Zheng, Shao-Liang; Chen, Yu-Sheng et al. (2017) The Crystalline Sponge Method: A Solvent-Based Strategy to Facilitate Noncovalent Ordered Trapping of Solid and Liquid Organic Compounds. CrystEngComm 19:4528-4534 |
| Gemperline, Erin; Horn, Heidi A; DeLaney, Kellen et al. (2017) Imaging with Mass Spectrometry of Bacteria on the Exoskeleton of Fungus-Growing Ants. ACS Chem Biol 12:1980-1985 |
| Wyche, Thomas P; Ruzzini, Antonio C; Schwab, Laura et al. (2017) Tryptorubin A: A Polycyclic Peptide from a Fungus-Derived Streptomycete. J Am Chem Soc 139:12899-12902 |
| Adnani, Navid; Rajski, Scott R; Bugni, Tim S (2017) Symbiosis-inspired approaches to antibiotic discovery. Nat Prod Rep 34:784-814 |
| Ruzzini, Antonio C; Clardy, Jon (2016) Gene Flow and Molecular Innovation in Bacteria. Curr Biol 26:R859-R864 |
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