The role of LytR-CpsA-Psr proteins in cell envelope biogenesis of Mycobacterium smegmatis

Tuberculosis infection is one of the leading causes of mortality worldwide and is caused by Mycobacterium tuberculosis (Mtb). With an upsurge of multidrug-resistant tuberculosis, it is a global threat. Therefore, development of new drugs need immediate attention, and this needs identification of potential drug targets. The cell envelope of mycobacteria is one such attractive drug target owing to its role in maintaining the structural integrity and pathogenicity of the bacterium. The LytR-CpsA-Psr (LCP) family of proteins in Mycobacterium spp. have been shown to catalyze the coupling of arabinogalactan and peptidoglycan and possess pyrophosphatase activity. The four LCP protein homologues present in Mycobacterium smegmatis (Msmeg), MSMEG_0107, MSMEG_1824, MSMEG_5775 and MSMEG_6421, have not been extensively investigated with the focus on the existence and interplay of multiple LCP proteins. In this study with this non-pathogenic model organism, all four LCP homologues were shown to possess pyrophosphatase activity, with a significant higher activity displayed by MSMEG_0107 and MSMEG_5775. In order to further study the role of the LCP proteins on the physiology of the bacterium, single and double deletion strains ... (continues)