Evaluation of the OSMAC approach in marine bacteria to investigate the anti-Trypanosoma cruzi potential

• Grant number: 21/03392-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2021
• End date: December 31, 2021
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: André Gustavo Tempone Cardoso
• Grantee: Beatriz Alves de Andrade
• Host Institution: Instituto Adolfo Lutz (IAL). Coordenadoria de Controle de Doenças (CCD). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

The "One Strain Many Compounds" (OSMAC) approach is a cultivation-based strategy, which aims to provide a simple and promising tool, with the ability to stimulate the expression of cryptic genes in microorganisms. This approach highlights how a single microbial strain can produce different biomolecules when grown under different environmental conditions. Auxiliary metabolites by microorganisms represent a promising source of new pharmaceutical prototypes, many of which are active as antimicrobials. Marine bacteria have a high chemiodiversity, still little explored for the selection of bioactive compounds against neglected parasitic diseases. Among the most important neglected diseases, Chagas disease affects 7 million people, with only one drug with low efficacy and high toxicity. The selection of new compounds as drug candidates is a must. The present project aims to study the potential of marine bacteria for the production of new anti-Trypanosoma cruzi compounds, using an OSMAC approach. Marine bacteria will be identified by mass spectrometry (MALDI TOF-MS) and cultured to obtain extracts containing their secondary metabolites. The antiparasitic activity will be provided in vitro through the Effective Concentration 50% (EC50). The marine strain that presents the most potent extract, will be grown under different conditions, varying sources of carbon and nitrogen, as well as in the presence of antigens of the parasite in the culture medium. Under the ideal OSMAC condition, marine microbial extracts will again be prepared and studied for potency in vitro against T. cruzi. To evaluate the profile of the active bacterial metabolites obtained under different culture conditions, the organic extracts will be performed using high performance liquid chromatography and Nuclear Magnetic Resonance, with advanced dereplication. Therefore, this study may contribute to the evaluation of the pharmacological potential of secondary metabolites from marine bacteria, specific future pharmaceutical prototypes for Chagas disease.