1: J Bacteriol. 2008 Dec;190(24):7904-9. Epub 2008 Oct 3. Direct observation of Staphylococcus aureus cell wall digestion by lysostaphin. Francius G, Domenech O, Mingeot-Leclercq MP, Dufrêne YF. Unité de Chimie des Interfaces, Université Catholique de Louvain, Louvain-la-Neuve, Belgium. The advent of Staphylococcus aureus strains that are resistant to virtually all antibiotics has increased the need for new antistaphylococcal agents. An example of such a potential therapeutic is lysostaphin, an enzyme that specifically cleaves the S. aureus peptidoglycan, thereby lysing the bacteria. Here we tracked over time the structural and physical dynamics of single S. aureus cells exposed to lysostaphin, using atomic force microscopy. Topographic images of native cells revealed a smooth surface morphology decorated with concentric rings attributed to newly formed peptidoglycan. Time-lapse images collected following addition of lysostaphin revealed major structural changes in the form of cell swelling, splitting of the septum, and creation of nanoscale perforations. Notably, treatment of the cells with lysostaphin was also found to decrease the bacterial spring constant and the cell wall stiffness, demonstrating that structural changes were correlated with major differences in cell wall nanomechanical properties. We interpret these modifications as resulting from the digestion of peptidoglycan by lysostaphin, eventually leading to the formation of osmotically fragile cells. This study provides new insight into the lytic activity of lysostaphin and offers promising prospects for the study of new antistaphylococcal agents. PMCID: PMC2593208 [Available on 2009/06/01] PMID: 18835985 [PubMed - indexed for MEDLINE] Related Links epr, which encodes glycylglycine endopeptidase resistance, is homologous to femAB and affects serine content of peptidoglycan cross bridges in Staphylococcus capitis and Staphylococcus aureus. [J Bacteriol. 1997] PMID:9209049 Cell wall composition and decreased autolytic activity and lysostaphin susceptibility of glycopeptide-intermediate Staphylococcus aureus. [Antimicrob Agents Chemother. 2004] PMID:15388430 Lysostaphin: an antistaphylococcal agent. [Appl Microbiol Biotechnol. 2008] PMID:18607587 Staphylococcus aureus mutants with increased lysostaphin resistance. [J Bacteriol. 2006] PMID:16923896 Lysostaphin disrupts Staphylococcus aureus and Staphylococcus epidermidis biofilms on artificial surfaces. [Antimicrob Agents Chemother. 2003] PMID:14576095