Abstract

Staphylococcus aureus secretes autolysin (Atl) to complete cell division by hydrolyzing its thick cell wall layer at a designated site, known as the equatorial surface ring. Secreted pro-Atl (1256 amino acids) is cleaved at residues 198 and 775 to generate a pro-peptide, amidase and glucosaminidase, respectively. Here we examined the mechanism that directs amidase and glucosaminidase to the cell division site on the staphylococcal surface. Targeting of pro-Atl to the cell surface occurred prior to its proteolytic processing. Three repeat domains (R1, R2 and R3) located at the center of pro-Atl are necessary and sufficient for the targeting of reporter proteins to the equatorial surface ring. Pro-Atl cleavage at residue 775 separates the polypeptide such that R1 and R2 are linked to the C-terminus of amidase, whereas R3 is located at the N-terminus of glucosaminidase. Thus, it appears that the repeat domains direct pro-Atl, amidase and glucosaminidase to a specific receptor at the equatorial surface ring of staphylococci, thereby allowing localized peptidoglycan hydrolysis and separation of the dividing cells.