Study of the NlpC_P60-like enzymes for the development of novel antimycobacterial agents

• Grant number: 24/15878-6
• Support Opportunities: Scholarships in Brazil - Support Program for Fixating Young Doctors
• Start date: October 01, 2024
• End date: September 30, 2025
• Field of knowledge: Biological Sciences - Biochemistry - Biochemistry of Microorganisms
• Principal Investigator: Marcio Vinicius Bertacine Dias
• Grantee: Catharina dos Santos Silva
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 24/02235-0 - Study of the NlpC_P60-like enzymes for the development of novel antimycobacterial agents, AP.R

Abstract

The main function of the bacterial cell wall is to maintain the shape and integrity of the cell. However, far from being a static structure, the cell wall undergoes constant remodeling and modifications throughout the cell cycle. The peptidoglycan layer is one of the main components of the bacterial cell wall. Therefore, the balance between peptidoglycan synthesis and degradation during cell growth and division processes is crucial for bacterial viability and proliferation. Thus, the factors involved in controlling peptidoglycan biosynthesis are interesting targets for drug development. Members of the NlpC_P60 superfamily of peptidases are involved in the control of these physiological processes as well as in the pathogenesis of several bacterial lineages. However, the knowledge about mycobacterial NlpC_P60 proteins is still limited, despite the great progress in recent years. In view of this, the present research project aims to study the structural biology of the uncharacterised activated NlpC_P60 enzymes from clinically important mycobacteria and apply the fragment-based drug discovery strategy against these potential targets in the search for new antimycobacterial agents.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SILVA, CATHARINA DOS SANTOS; DIAS, MARCIO VINICIUS BERTACINE. The multiple roles of the NlpC_P60 peptidase family in mycobacteria - an underexplored target for antimicrobial drug discovery. FEBS Letters, v. N/A, p. 19-pg., 2025-03-03. (24/02235-0, 22/12234-5, 20/03850-9, 16/18721-4, 21/10577-0, 24/15878-6)