Tertiary Structure of Staphylococcus aureus Cell Wall Murein

Abstract

Staphylococcus aureus is an important human pathogen that causes life-threatening diseases including septicemia, endocarditis, toxic shock syndrome, and abscesses in organ tissues (15,25). The cell wall of the microorganism plays an important role in infectivity and pathogenicity (40). Over several decades of research, extensive knowledge has accumulated concerning epidemiology (9), virulence (25, 28), genetics (3), genomic evolution (14), the biochemistry of cell wall assembly (31), the crystal structures of ␤-lactam-resistant enzymes (24), the ultrastructure of the cell wall (4, 18), and the muropeptide composition of wild-type, methicillin-resistant (7), and vancomycinresistant strains (34). Nonetheless, the tertiary molecular structure of the cell wall, which is central for understanding cell growth and division in staphylococci, has remained elusive. As a consequence, there is no graphic illustration of the wall architecture in the literature that adequately represents known physicochemical details of staphylococcal peptidoglycan.Staphylococci are gram-positive bacteria, and their cell walls are composed of murein (32, 38, 41), teichoic acids (2), and wall-associated surface proteins (20,26,30). Stress-bearing murein represents a continuous macromolecular sacculus covering the whole cell. Murein consists of glycan strands, which are cross-linked by peptide bridges furnishing the structural integrity of the sacculus. It is a distinctive feature of staphylococci that the observed degree of murein cross-linking, which was determined as a ratio of bridged peptides to the total amount of all peptide ends in general, is extremely high, on the order of 80 to 90% (16, 35).Glycan strands in staphylococcal murein are composed of N-acetylglucosamine (GlcpNAc) and N-acetylmuramic acid (MurpNAc) residues that furnish ␤-(134)-linked disaccharide repeating units, with MurpNAc representing the reducing terminus of the chain. The carboxyl group of each MurpNAc residue is amidated by the stem pentapeptide L-Ala-D-isoGln-L-Lys-D-Ala-D-Ala, and the ε-amino group of the lysine residue is substituted with a pentaglycine appendage (37). Thus, each peptide attached to a MurpNAc residue is a branched decapeptide with an amino group on the Gly and a carboxyl group on the D-Ala terminus, and arms of the peptide side chains interact with each other to provide a high degree of murein cross-linking. Although the general principle of murein structural organization is simple, the muropeptide composition of the staphylococcal sacculi appears very complex, as a standard digestion of sacculi with muramidase (the enzyme that cleaves MurpNAc glycosidic bonds) releases more than 20 distinct components plus an unresolved material. The latter makes up about 50 to 60% of the muropeptide-containing oligomers, with up to 20 repeating units (7,38). Thus, the major part of staphylococcal murein architecture could be envisaged as being constructed of interlinked glycan and oligopeptide chains, both varying in their lengths.On electron micrographs, the ...

Atomic force microscopy study of the antibacterial effect of fosfomycin on methicillin-resistant Staphylococcus pseudintermedius

“…The gram-positive cell is dense with about 20-80 nm thickness (Dmitriev et al 2004) and consists of numerous interconnecting layers of peptidoglycan. The chemical make-up of this cell wall consists of cables of cross-linked glycan strands of about 50 nm in width.…”

Reduced Vancomycin Susceptibility inStaphylococcus aureus, Including Vancomycin-Intermediate and Heterogeneous Vancomycin-Intermediate Strains: Resistance Mechanisms, Laboratory Detection, and Clinical Implications

“…1). Under the capsule lies the cell wall, a structure composed of highly cross-linked peptidoglycan (PG) (a complex structure composed of sugars and amino acids, also called murein), teichoic acids, and cell wall-associated proteins (72). The peptidoglycan is composed of glycan chains made up of the alternating amino sugars N-acetylglucosamine and Nacetylmuramic acid.…”

“…Teichoic acid chains are attached to the 6-hydroxyl groups of some of the N-acetylmuramic acid residues of the glycan chains and, together with the peptidoglycan, form a multilayered network that surrounds the S. aureus cell (161,351). The stress-bearing murein therefore represents a continuous macromolecule encasing the sacculus (72). Typically, the degree of murein cross-linking in the S. aureus cell wall is high, with bridged peptides as a ratio of all peptide ends in the order of 80 to 90% (72,328).…”

Peptidoglycan architecture can specify division planes in Staphylococcus aureus

“…In the absence of a cell wall, turgor pressure drives the cell towards the most energetically favourable conformation; a sphere 12 . Two possible paradigms for the nanoscale arrangement of glycan strands, the peptidoglycan structure, have been proposed: arrangement of glycan strands in the plane of the cytoplasmic membrane 13 or in a scaff old perpendicular to the cytoplasmic membrane 14,15 . Th e glycan chain lengths in S. aureus are suffi ciently short to permit either of these confi gurations 16 .…”