Mycobacteria recycle their peptidoglycan via a novel pathway which influences antimicrobial resistance and limits proliferation in macrophages.

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 for the first time that M. tuberculosis and Mycobacterium bovis BCG are able to recycle components of their PG. We demonstrate that the core-mycobacterial gene lpqI, encodes an authentic NagZ {beta}-N-acetylglucosaminidase and that it is essential for PG-derived amino sugar recycling via an unusual pathway. By characterizing an M. bovis BCG strain lacking lpqI we are also able to show that stem-peptide recycling proceeds independent of amino sugar recovery and loss of lpqI leads to antimicrobial resistance in vitro. Together these data provide a critical first step in understanding how mycobacteria recycle their peptidoglycan.