Abstract
Growth and division by most bacteria requires remodeling and cleavage of their cell wall. A byproduct of this process is the generation of free peptidoglycan (PG) fragments known as muropeptides. These muropeptides are recycled in many model organisms, where the bacteria can harness their unique nature as a signal for cell wall damage. These molecules also serve as important signals for hosts where binding to specific receptors reports on the presence of intracellular bacteria. Despite this critical role for muropeptides, it has long been thought that pathogenic mycobacteria such as Mycobacterium tuberculosis do not recycle their PG. Herein we show that M. tuberculosis and Mycobacterium bovis BCG are both able to recycle components of their PG. We demonstrate that MurNAc but not GlcNAc can be metabolised by mycobacteria and that stem-peptide recycling proceeds independent of amino sugar recovery. In addition, we demonstrate that the core-mycobacterial gene lpqI encodes an authentic NagZ β-N-acetylglucosaminidase, which is essential for recycling MurNAc. Surprisingly, loss of lpqI leads to antimicrobial resistance and increased proliferation in macrophages. This supports a model whereby the amount of PG released by mycobacterial cells is tightly controlled in order to effectively modulate the infection process.