A molecular link between cell wall biosynthesis, translation fidelity, and stringent response in <i>Streptococcus pneumoniae</i>
Surya D. Aggarwal, Adrian J. Lloyd, Saigopalakrishna S. Yerneni, Ana Rita Narciso, Jennifer N. Shepherd, David I. Roper, Christopher G. Dowson, Sérgio R. Filipe, N. Luisa Hiller
Abstract
Significance During infection, microbes must survive the hostile environmental conditions of the human host. When exposed to stresses, bacteria activate an intracellular response, known as the stringent response pathway, to ensure their survival. This study connects two fundamental pathways important for cellular growth in a Gram-positive pathogen: it demonstrates that enzymes responsible for cell wall biosynthesis are connected to the stringent response pathway via their ability to ameliorate errors in protein translation. Our study was performed on S. pneumoniae , where the MurM cell wall biosynthesis enzyme, a tRNA-dependent amino acyl transferase, is linked to penicillin resistance. We now demonstrate the importance of MurM in translation quality control and establish that it serves as a gatekeeper of the stringent response pathway.