Abstract
The envelope of Staphylococcus aureus is comprised of peptidoglycan and its attached secondary polymers, teichoic acid, capsular polysaccharide, and protein. Peptidoglycan synthesis involves polymerization of lipid II precursors into glycan strands that are cross-linked at wall peptides. It is not clear whether peptidoglycan structure is principally determined during polymerization or whether processive enzymes affect cell wall structure and function, for example, by generating conduits for protein secretion. We show here that S. aureus lacking SagB, a membrane-associated N-acetylglucosaminidase, displays growth and cell-morphological defects caused by the exaggerated length of peptidoglycan strands. SagB cleaves polymerized glycan strands to their physiological length and modulates antibiotic resistance in methicillin-resistant S. aureus (MRSA). Deletion of sagB perturbs protein trafficking into and across the envelope, conferring defects in cell wall anchoring and secretion, as well as aberrant excretion of cytoplasmic proteins. Importance: Staphylococcus aureus is thought to secrete proteins across the plasma membrane via the Sec pathway; however, protein transport across the cell wall envelope has heretofore not been studied. We report that S. aureus sagB mutants generate elongated peptidoglycan strands and display defects in protein secretion as well as aberrant excretion of cytoplasmic proteins. These results suggest that the thick peptidoglycan layer of staphylococci presents a barrier for protein secretion and that SagB appears to extend the Sec pathway across the cell wall envelope.