Perturbation of cell wall synthesis suppresses autolysis in Staphylococcus aureus: Evidence for coregulation of cell wall synthetic and hydrolytic enzymes

Bacterial pepticloglycan hydrolases are considered to have destructive potential, which in the presence of inhibitory concentrations of cell wall synthesis inhibitors is involved in cell lysis. Therefore, the expression and activity of autolytic enzymes must be tightly regulated in growing cells. We describe here a series of experiments undertaken to examine further the coordination between cell wall synthesis and degradation. Cell growth in the presence of subinhibitory concentrations of R-lactam antibiotics was used to determine the effects of the partial inhibition of cell wall synthesis on the status of the autolytic system in Staphylococcus aureus. Our results revealed that, despite increased in vitro hydrolysis of cell walls by autolytic enzymes due to hypo-cross-linked peptidoglycans, cells grown in the presence of beta-lactams were dramatically less prone to autolysis as a result of decreased transcription and enzymatic activities of several major autolytic enzymes. Similar repression of autolytic enzymatic activity and transcription was also observed when cell wall synthesis was disturbed by lowering the level of transcription of pbpB, the gene encoding the major transpeptidase in S. aureus. Our data show that the perturbation of cell wall synthesis in growing cells of S. aureus induces strong repression of the autolytic system and provide evidence for transcriptional regulation between cell wall synthetic and hydrolytic enzymes.