A new regulator of the Staphylococcus aureus peptidoglycan hydrolase Sle1

Regulation of peptidoglycan hydrolases is crucial for bacterial cell integrity, growth and division. In the bacterial pathogen Staphylococcus aureus, the amidase Sle1 is a key autolysin required for septum splitting and daughter cell separation. Through genetic suppressor screening, we have identified CxaR, a previously uncharacterized protein, as a novel negative regulator of Sle1. In the absence of CxaR, cellular levels of Sle1 increase nearly ten-fold, resulting in premature splitting of the division septum and increased cell lysis during exponential growth. CxaR localizes to the division septum, late in septum synthesis, and this localization requires both the divisome protein FtsK and the ClpX component of the ClpXP proteolytic machinery. We propose that CxaR promotes ClpXP-mediated degradation of Sle1 towards the end of the cell cycle.