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

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.