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

## TL;DR

This review explores the NlpC_P60 peptidase family in mycobacteria, highlighting their roles in cell wall processes and potential as targets for new antibiotics.

## Contribution

The paper compiles current knowledge on mycobacterial NlpC_P60 proteins, emphasizing their underexplored potential for antimicrobial drug discovery.

## Key findings

- NlpC_P60 peptidases are involved in cell wall homeostasis and pathogenesis in mycobacteria.
- Knowledge gaps exist regarding the distribution and function of these proteins across Mycobacterium species.
- These peptidases show potential as novel targets for drug development.

## 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.

The NlpC_P60 superfamily of peptidases is recognised by its key role in bacterial cell wall homeostasis. Recently, studies have also described the involvement of NlpC_P60‐like enzymes in bacterial competitive mechanisms and pathogenesis across several lineages. In our Review, we provided compiled information about the mycobacterial NlpC_P60 proteins, shedding light on the underexplored potential of these peptidases as targets for drug design campaigns.