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Natural metabolites for treating antimicrobial resistant gonorrhoea and visceral leishmaniasis

Grant number: 18/26655-7
Support type:Regular Research Grants
Duration: September 01, 2019 - August 31, 2021
Field of knowledge:Biological Sciences - Parasitology
Cooperation agreement: University of Southampton
Mobility Program: SPRINT - Projetos de pesquisa - Mobilidade
Principal Investigator:André Gustavo Tempone Cardoso
Grantee:André Gustavo Tempone Cardoso
Principal investigator abroad: Myron Christodoulides
Institution abroad: University of Southampton, England
Home Institution: Instituto Adolfo Lutz (IAL). Coordenadoria de Controle de Doenças (CCD). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
Partner institutions: University of Southampton
Assoc. researchers:João Henrique Ghilardi Lago
Associated research grant:18/10279-6 - Selection and optimization of new drug candidates for Leishmaniasis and Chagas Disease, AP.R

Abstract

Neisseria gonorrhoeae (Ng, gonococcus) is the causative agent of the sexually transmitted disease gonorrhoea and affects 78 million people worldwide. Gonococcal infection is frequently asymptomatic but long-term and/or permanent sequelae can develop in individuals. Effective, accessible and affordable antimicrobial treatment is essential for management and control. However, gonococci have evolved resistance to all antimicrobials for gonorrhea treatment and the organism now has earned the epithet of 'Superbug'. Among neglected diseases, leishmaniasis is a protozoan neglected disease that affects approximately 12 million people worldwide. The visceral form (VL) is fatal if untreated and is estimated to cause about 50,000 deaths each year. Chemotherapy remains the most important element in the control of VL, and is highly toxic and shows low efficacy. New treatments are needed. Natural metabolites from plants and microorganisms are a powerful tool for the design of new medicines. The Brazilian flora has been considered a promising source of these small molecules. Among microorganisms, terrestrial and marine bacteria offer an enormous chemo-diversity and have been shown to produce powerful antimicrobial compounds to be used as new scaffolds for Drug Discovery. In this proposal, we aim to explore this link between molecular structure and bioactivity to directly connect biodiversity to the discovery of new medicines. As part of the ongoing FAPESP project 2018/10279-6, Prof. Tempone and Prof. Lago generated a bank of bioactive natural compounds to be used in a lead optimization program for leishmaniasis and Chagas disease. Then, pure and chemically characterized plant metabolites will be tested against resistant strains of Neisseria gonorrhoea at the University of Southampton. In the search for new natural scaffolds for VL, microbial metabolites isolated from different sources, including marine bacteria from Southampton (UK) sea sediments and from pathogenic species of Neisseria sp., will be investigated for the potential antiparasitic activity. Selected bioactive extracts will be subjected to dereplication procedures using LC/MS and NMR to identify the microbial metabolites. By using bio-guided fractionation, active compounds will be isolated and chemically characterized by spectrometric and spectroscopic analysis. We propose to use this pump-priming application as a springboard for studying long-term objectives through the generation of pilot data and collaboration between our groups and institutions. (AU)