The multiple roles of the NlpC_P60 peptidase family in mycobacteria - an underexplored target for antimicrobial drug discovery

Author(s)

Silva, Catharina dos Santos ; Dias, Marcio Vinicius Bertacine

• Document type: Journal article
• Source: FEBS Letters; v. N/A, p. 19-pg., 2025-03-03.

Abstract

The main function of the cell wall is to maintain cellular integrity throughout the cell cycle by keeping the cell shape during growth and division. However, far from being a static structure, the cell wall undergoes constant recycling and even molecular modifications of its components. The major component of the bacterial cell wall is the peptidoglycan layer. The balance between peptidoglycan synthesis and degradation is crucial for cell viability and proliferation. Hence, factors involved in the control of peptidoglycan turnover are considered interesting targets for drug development. Members of the NlpC_P60 superfamily of peptidases have been described to participate in the physiology and pathogenesis of several bacterial lineages. However, the knowledge about NlpC_P60-like proteins from mycobacteria is still limited, despite the great progress in recent years. In this Review, we aimed to compile the information about mycobacterial NlpC_P60 proteins, pointing out their distribution across pathogenic and environmental Mycobacterium species, highlighting the knowledge gaps and describing their structural features, role in the physiology and mycobacterial pathogenesis. (AU)

• FAPESP's process: 24/02235-0 - Study of the NlpC_P60-like enzymes for the development of novel antimycobacterial agents
• Grantee: Marcio Vinicius Bertacine Dias
• Support Opportunities: Regular Research Grants
• FAPESP's process: 22/12234-5 - Resistance to antimicrobials in Mycobacterium tuberculosis: structural, biophysical and biochemical analysis of missense mutations
• Grantee: Marcio Vinicius Bertacine Dias
• Support Opportunities: Regular Research Grants
• FAPESP's process: 20/03850-9 - Mycobacterium cell wall: structural studies and inhibition strategies for enzymes involved in the biosynthesis and regulation
• Grantee: Marcio Vinicius Bertacine Dias
• Support Opportunities: Regular Research Grants
• FAPESP's process: 16/18721-4 - Structural basis of the elongation and cell division control in Mycobacterium tuberculosis and identification of new drug hits based in fragment trials
• Grantee: Catharina dos Santos Silva
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 21/10577-0 - Biology of Bacteria and Bacteriophages Research Center
• Grantee: Shaker Chuck Farah
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 24/15878-6 - Study of the NlpC_P60-like enzymes for the development of novel antimycobacterial agents
• Grantee: Catharina dos Santos Silva
• Support Opportunities: Scholarships in Brazil - Support Program for Fixating Young Doctors