Novel therapeutic agents from the bacterial symbionts of Brazilian invertebrates

Harvard Medical School, Boston MA

Investigators

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Abstract

AP1 PROJECT SUMMARY/ABSTRACT 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.