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Natural inhibitors of Penicillin-Binding Proteins (PBPs) from marine microorganisms and invertebrates: isolation, identification and mechanism of action

Grant number: 19/26892-1
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Effective date (Start): June 01, 2020
Effective date (End): October 31, 2021
Field of knowledge:Physical Sciences and Mathematics - Chemistry - Organic Chemistry
Principal Investigator:Roberto Gomes de Souza Berlinck
Grantee:Felipe Hilário
Host Institution: Instituto de Química de São Carlos (IQSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil
Associated research grant:13/50228-8 - Biodiversity components, and their metabolic characters, of Brazilian Islands: an integrated approach, AP.BTA.TEM

Abstract

The global crisis of bacterial resistance has intensified dramatically in recent years and threatens the maintenance of society's public health standards. This is the result of overuse and inappropriate use of antibiotics, inadequate medical practices, lack of effective regulation in many countries, and the lack of discovery of new antibiotics by pharmaceutical companies. Microorganisms are an inexhaustible source of natural products that have given rise to most antibiotics used to treat infections. Two of the most important peptide glycan biosynthesis reactions, the main constituent of the bacterial cell wall, are performed by enzymes called Penicillin-Binding Proteins (PBPs). Because of their accessible location and critical function, they are the specific target of ²-lactam antibiotics. Aiming at the discovery of new antibiotics, a library of extracts and fractions of natural products produced by different (micro) organisms was tested in fluorescence polarization assays of a PBP using a fluorescent ²-lactam. About 30 hits were identified, aiming at isolation, structural elucidation and evaluation of the mechanism of action of antibiotic activity of new natural PBPs inhibitor metabolites of strains susceptible and resistant to beta-lactam antibiotics. (AU)

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