Suppressor mutations linking gpsB with the first committed step of peptidoglycan biosynthesis in Listeria monocytogenes

摘要: The cell division protein GpsB is a regulator of the penicillin binding A1 (PBP A1) in Gram-positive human pathogen Listeria monocytogenes Penicillin proteins mediate last two steps peptidoglycan biosynthesis as they polymerize and cross-link strands, main components bacterial wall. It not known what other processes are controlled by GpsB. L. gpsB mutants unable to grow at 42°C, but we observed that spontaneous suppressors correcting this defect arise on agar plates with high frequency. We here describe first set mapped clpC murZ genes. While ClpC ATPase component Clp protease, MurZ paralogue listerial UDP-N-acetylglucosamine (UDP-GlcNAc) 1-carboxyvinyltransferase MurA. Both enzymes catalyze enolpyruvyl transfer from phosphoenolpyruvate UDP-GlcNAc, representing committed step biosynthesis. confirmed clean deletion or gene suppressed ΔgpsB phenotype. turned out absence either leads accumulation MurA, show artificial overexpression MurA alone was sufficient for suppression. Inactivation UDP-GlcNAc-consuming pathways also heat-sensitive growth mutant, suggesting an increased influx precursor molecules into can compensate lack Our results support model according which PBP becomes misregulated thus toxic due unproductive consumption wall molecules. Importance late important bacteria. interacts one key pathway, A1), influences its activity. catalyzes biosynthesis, it unknown how controls A1. mutant forms have their mutations genes mediating influencing likely stimulating metabolites pathway. assume ensure productive incorporation precursors sacculus