Cell wall assembly in Staphylococcus aureus: proposed absence of secondary crosslinking reactions

Gally, David L.; Ar, Archibald

doi:10.1099/00221287-139-8-1907

Cited by 29 publications

(31 citation statements)

References 16 publications

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“…Nevertheless, detailed analysis of peptidoglycan treated with mutanolysin (21, 224) or ⌽11 hydrolase (137) revealed only a very limited degree of cross-linking between IsdC anchor peptides compared to that between the anchor peptides generated by sortase A (115,137). About 80 to 95% of all murein subunits of assembled peptidoglycan harbor cell wall tetrapeptides with cross-linked D-Ala at position four (57,184,188), and this can also be observed for sortase A-anchored surface proteins, which are embedded at any position in glycan chains with up to 11 MurNAc-GlcNAc disaccharide units and cross-linked to as many as 15 cell wall peptides (137). In contrast, sortase B-anchored product is attached to at most six or seven disaccharide subunits, and its wall peptides are either non-cross-linked (murein petapeptides) or linked to two or three peptidoglycan subunits (Fig.…”

Section: Biochemistry Of the Sortase B Reactionmentioning

confidence: 99%

Sortases and the Art of Anchoring Proteins to the Envelopes of Gram-Positive Bacteria

Marraffini

DeDent²,

Schneewind³

2006

Microbiol Mol Biol Rev

610

600

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SUMMARY The cell wall envelopes of gram-positive bacteria represent a surface organelle that not only functions as a cytoskeletal element but also promotes interactions between bacteria and their environment. Cell wall peptidoglycan is covalently and noncovalently decorated with teichoic acids, polysaccharides, and proteins. The sum of these molecular decorations provides bacterial envelopes with species- and strain-specific properties that are ultimately responsible for bacterial virulence, interactions with host immune systems, and the development of disease symptoms or successful outcomes of infections. Surface proteins typically carry two topogenic sequences, i.e., N-terminal signal peptides and C-terminal sorting signals. Sortases catalyze a transpeptidation reaction by first cleaving a surface protein substrate at the cell wall sorting signal. The resulting acyl enzyme intermediates between sortases and their substrates are then resolved by the nucleophilic attack of amino groups, typically provided by the cell wall cross bridges of peptidoglycan precursors. The surface protein linked to peptidoglycan is then incorporated into the envelope and displayed on the microbial surface. This review focuses on the mechanisms of surface protein anchoring to the cell wall envelope by sortases and the role that these enzymes play in bacterial physiology and pathogenesis.

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Section: Biochemistry Of the Sortase B Reactionmentioning

confidence: 99%

Sortases and the Art of Anchoring Proteins to the Envelopes of Gram-Positive Bacteria

Marraffini

DeDent²,

Schneewind³

2006

Microbiol Mol Biol Rev

610

600

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“…The square hole thus obtained possessed 484 positions for the glycan strands and was flanked along the perimeter by the existing fabric to allow incoming strands to cross-link with it, thus making the simulated process in agreement with murein assembly in vivo (16,39). The maximal height of the matrix was considered to be about 45 disaccharides in order to guarantee the true thickness of the S. aureus cell walls observed in experiments omitting the procedures of fixation and staining (12).…”

Section: Definitionsmentioning

confidence: 99%

“…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).…”

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confidence: 99%

Tertiary Structure of Staphylococcus aureus Cell Wall Murein

et al. 2004

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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 ...

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“…PBPs are enzymes involved in the final stages of PGN biosynthesis, which synthesize glycan chains (via transglycosylation reactions) and cross-link different glycan chains through short peptides (via transpeptidation reactions). The level of PGN cross-linking varies between bacterial species, and S. aureus has an unusually high degree of cross-linking (23), which is due mainly to the action of PBP4 (24,25), and seems to require the long and flexible pentaglycine crossbridge that S. aureus cells use to connect two stem peptides from different glycan strands (23,26). PBP4 is not essential for S. aureus viability.…”

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confidence: 99%

Teichoic acids are temporal and spatial regulators of peptidoglycan cross-linking in Staphylococcus aureus

Atilano¹,

Pereira

Yates³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

237

309

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The cell wall of Staphylococcus aureus is characterized by an extremely high degree of cross-linking within its peptidoglycan (PGN). Penicillin-binding protein 4 (PBP4) is required for the synthesis of this highly cross-linked peptidoglycan. We found that wall teichoic acids, glycopolymers attached to the peptidoglycan and important for virulence in Gram-positive bacteria, act as temporal and spatial regulators of PGN metabolism, controlling the level of cross-linking by regulating PBP4 localization. PBP4 normally localizes at the division septum, but in the absence of wall teichoic acids synthesis, it becomes dispersed throughout the entire cell membrane and is unable to function normally. As a consequence, the peptidoglycan of TagO null mutants, impaired in wall teichoic acid biosynthesis, has a decreased degree of cross-linking, which renders it more susceptible to the action of lysozyme, an enzyme produced by different host organisms as an initial defense against bacterial infection.

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Cell wall assembly in Staphylococcus aureus: proposed absence of secondary crosslinking reactions

Cited by 29 publications

References 16 publications

Sortases and the Art of Anchoring Proteins to the Envelopes of Gram-Positive Bacteria

Sortases and the Art of Anchoring Proteins to the Envelopes of Gram-Positive Bacteria

Tertiary Structure of Staphylococcus aureus Cell Wall Murein

Teichoic acids are temporal and spatial regulators of peptidoglycan cross-linking in Staphylococcus aureus

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