Identification of the mode of action of a quinazoline with antimicrobial activity against phytopathogenic Xanthomonas species

• Grant number: 21/00583-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: May 01, 2021
• End date: January 31, 2022
• Field of knowledge: Biological Sciences - Genetics - Molecular Genetics and Genetics of Microorganisms
• Principal Investigator: Celso Eduardo Benedetti
• Grantee: Thiago Gaspar Inácio
• Host Institution: Centro Nacional de Pesquisa em Energia e Materiais (CNPEM). Ministério da Ciência, Tecnologia e Inovação (Brasil). Campinas , SP, Brazil

Abstract

Given the relevance of Gram-negative bacteria as critical plant and animal pathogens, our group has synthetized and tested several quinazoline derivatives with antimicrobial action against these microorganisms. One such compound, named QX1, showed antimicrobial activity against several Xanthomonas pathogens. Although the antimicrobial activity of many quinazoline compounds is known, the primary mode of action of this class of molecules remains elusive. Therefore, the main goal of this project is to determine the mode of action of QX1 using Xanthomonas citri as a Gram-negative model. For this purpose, we have identified, by mass spectrometry, several X. citri proteins whose synthesis was enhanced in the presence of QX1 possibly in order to compensate for a metabolic pathway blockage caused by the compound. The identification of such proteins and the study of their biological function will help to clarify the QX1 mode of action. Thus, major X. citri proteins induced by QX1 were selected as direct targets of QX1 for functional and structural studies. In addition, because the chemical properties of QX1 have not yet been investigated in detail, and in order to support future studies with human bacterial pathogens, we intend to carry out cytotoxicity tests with QX1 in human cells.