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]

    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]