Peptidoglycan biosynthesis is a target for various antibiotics. Therefore, a large number of resistance mechanisms have evolved. Resistance strategies include changing the peptide structure of peptidoglycan. For example, replacing the terminal d-Ala-d-Ala with d-Ala-d-Lac confers resistance against vancomycin- and penicillininsensitive l,d-transpeptidases and leads to l,d- instead of d,d-cross-links. Activation of the 'cell-wall stress stimulon' by antibiotics results in overexpression of peptidoglycan biosynthesis-associated genes, suggesting a higher biosynthesis rate in order to cope with damages of the cell wall.

from Ute Bertsche in Bacterial Polysaccharides

Further reading: Bacterial Polysaccharides: Current Innovations and Future Trends

Labels: antibiotic resistance, peptidoglycan

The main purpose of the peptidoglycan sacculus is to maintain bacterial shape and to counteract the internal pressure of the bacterial cell, which is approximately 3–5 atm in Gram-negative bacteria and up to 25 atm in Gram-positive bacteria. This is reflected by the thickness of the peptidoglycan sacculus. Experimental evidence suggests that the sacculus is mainly single layered in Gram-negatives while Gram-positives have up to 40 layers of peptidoglycan.

Peptidoglycan also serves as an anchor for proteins. In Gram-negatives the only protein known to be covalently attached to the peptidoglycan is Braun's lipoprotein (Lpp), which links the sacculus to the outer membrane. Approximately one-third of the Lpp is covalently bound to the alpha-carboxyl-group of meso-diaminopimelic acid (m-A2pm) of the stem peptide by the episilon-amino group of the Lys at the Lpp C-terminus. The other two-thirds are freely associated with the outer membrane. Covalent binding is achieved by an l,d-transpeptidase reaction catalysed by three different proteins: ErfK, YcfS and YbiS, of which the latter seems to convey the main transpeptidase activity. During stationary growth the abundance of the bound form increases. In Gram-positive bacteria, proteins, capsular polysaccharides, and teichoic acids are covalently and non-covalently associated with peptidoglycan. These molecules are responsible for bacteria–host interactions and virulence. The covalent attachment of proteins is mediated by sortases, which recognize a specific cell wall sorting signal (CWS) located in the C-terminus of the attached protein.

S. aureus contains two different sortases: SrtA, recognizing the CWS 'LPXTG', anchors at least 21 proteins to peptidoglycan including protein A (Spa), fibronectin-binding proteins (Fnbp) A and B, clumping factor (Clf) A and B, and collagen adhesion protein (Cna), all of which are responsible for the manifestation of infections. SrtA directly anchors the proteins to the murein precursor molecule lipid II in a two-step transacetylation reaction, thus forming an amide bond between threonine (Thr) of the LPXTG-motif and glycine (Gly) at position five of the pentaglycine-bridge. In many Gram-positive bacteria this pathway is universal.

The second sortase of S. aureus is SrtB, whose only substrate is the NPQTN-containing protein IsdC. This iron-uptake protein is attached to non-cross-linked Gly5 of mature peptidoglycan by an amide bond between Thr and Gly. In other Gram-positive bacteria sortases of the C-family polymerize fimbriae and pili and anchor them to the murein sacculus. Sortases of the d-family play a role in developmental processes, e.g. during sporulation of Bacillus anthracis and mycelium formation in Streptomyces coelicolor. The covalent amide bond is always formed between the Thr and the Gly5.

from Ute Bertsche in Bacterial Polysaccharides

Further reading: Bacterial Polysaccharides: Current Innovations and Future Trends

Labels: peptidoglycan

In almost all eubacteria the cytoplasmic membrane is surrounded by a bag-shaped macromolecule: the peptidoglycan or murein sacculus. In Gram-negative bacteria it is located within the periplasm between the cytoplasmic membrane and the outer membrane, while in Gram-positive bacteria the peptidoglycan forms the outermost part of the cell. Eubacteria known not to contain peptidoglycan are Planctomyces, mycoplasmas, Chlamydiae and Orientia (Rickettsia) tsutsugamushi.

Peptidoglycan has been studied for several decades and the chemical composition has long been solved. As the term 'peptidoglycan' suggests, it consists of polysaccharides (glycan strands) cross-linked by peptide moieties. The sacculus can be isolated as a whole and viewed under the electron microscope. Its shape corresponds exactly to the form of the original cell. Unfortunately, to date it has not been possible to actually visualize the fine structure of this macromolecule, resulting in controversial discussions about the orientation of the glycan strands relative to the rod axes. The peptidoglycan sacculus has to be elongated and divided during bacterial growth. As it is a stress-bearing structure several models have been described for a safe enlargement and separation.

As the peptidoglycan sacculus is a distinct feature of bacteria it is a target for several different kinds of bacteriolytic antibiotics. To cope with these stress factors, different resistance mechanisms have evolved, some of them changing the structure of the murein sacculus.

from Ute Bertsche in Bacterial Polysaccharides

Further reading: Bacterial Polysaccharides: Current Innovations and Future Trends

Labels: peptidoglycan

The peptidoglycan or murein sacculus is the stress-bearing structure of bacterial cells. It consists of glycan strands cross-linked by peptide bridges. Even though studies on murein have a very long tradition, it is not known how the glycan strands are actually arranged.

The chemical fine structure and the muropeptide composition of different Gram-negative and Gram-positive bacteria have been investigated in detail. Escherichia coli and Staphylococcus aureus are generally considered representatives for both Gram forms. During cell growth the stress-bearing structure has to be elongated and/or divided by the insertion of new and elimination of old material without losing its strength. Therefore multienzyme complexes containing both murein synthases and murein hydrolases have been postulated.

Peptidoglycan biosynthesis is the target for many antibiotics such as β-lactams, D-cycloserine and glycopeptide-antibiotics such as vancomycin. Bacteria have developed a number of different strategies for coping with antibiotic and osmotic stress.

from Ute Bertsche in Bacterial Polysaccharides: Current Innovations and Future Trends

Further reading:

1. Bacterial Polysaccharides
2. Microbial Production of Biopolymers and Polymer Precursors
3. Microbiology Books

Labels: antibiotic resistance, biopolymers, peptidoglycan, polysaccharides