Muramic acid bacterial peptidoglycan

The first known 1-carboxyethyl ether of a sugar was 2-amino-3-0-[(/ )-l-carboxyethyl]-2-deoxy-D-glucose or muramic acid (37). It is a component of the polysaccharide moiety of the peptidoglycan in the bacterial cell-wall. It is partially replaced by the mamo isomer, 2-amino-3-6>-[(/ )-l-carboxy-ethyl]-2-deoxy-D-mannose, in the peptidoglycan from Micrococcus lyso-deikticus. 

A. Fox and R. M. T. Rosario, Quantification of muramic acid, a marker for bacterial peptidoglycan in dust collected from hospital and home air-conditioning filters using gas-chromatography mass spectrometry. Indoor Air-Intemat. J. Air Quality Cl. 4 239 (1994). 

The structure of the native immunostimulatory MDPs was found to be IV-acetyl muramyl-L-alanyl-D-isoglutamine. (/V-Acetyl muramic acid is a base component of bacterial peptidoglycan.) Native TDM is a potent pyrogen and is too toxic for general use as an adjuvant. The molecular basis underlining MDP s adjuvanticity remains to be fully elucidated. Administration of MDP, however, is known to activate a number of cell types that play direct/indirect roles in immune function, and induces the secretion of various immunomodulatory cytokines (Table 13.14). 

Cycloserine (Fig- 4) is produced by several species of Streptomyces. One of the basic glycosyl components of the bacterial cell wall, n-acetyl-muramic acid (the product of Mur A and MurB), is modified by the addition of the first three amino acids sequentially by MurC, MurD and MurE enzymes. A dipeptide, D-alanyl-D-alanine is then added to make the pentapeptide. In bacteria, L-alanine is the native form and it is converted to D-alanine form by alanine racemase (Air). Two D-alanines are joined by D-ala-D-ala ligase (DdlA) to synthesize the dipeptide. Cycloserine resembles the substrate for Air and Ddl and inhibits their respective reactions in stage I of the peptidoglycan biosynthesis (Fig. 2). 

Figure 2 Mode of action of the prototypical lantibiotic nisin. (a) The peptidoglycan precursor lipid II is composed of an N-acetylglucosamine-p-1,4-N-acetylmuramic acid disaccharide (GIcNAc-MurNAc) that is attached to a membrane anchor of 11 isoprene units via a pyrophosphate moiety. A pentapeptide is linked to the muramic acid. Transglycosylase and transpeptidase enzymes polymerize multiple lipid II molecules and crosslink their pentapeptide groups, respectively, to generate the peptidoglycan. (b) The NMR solution structure of the 1 1 complex of nisin and a lipid II derivative in DMSO (6). (c) The amino-terminus of nisin binds the pyrophosphate of lipid II, whereas the carboxy-terminus inserts into the bacterial membrane. Four lipid II and eight nisin molecules compose a stable pore, although the arrangement of the molecules within each pore is unknown (5).

Bacterial polysaccharides can also serve as markers to identify specific bacterial species or genera. Typical microbial polysaccharides include peptidoglycans, lipopolysaccharides, and teichoic/teichuronic acids. Some markers such as muramic acid, D-alanine, and p-hydroxy myristic acid are present in the polysaccharides from eubacteria but are uncommon in higher life forms such as plants and animals. Pyrolysis results on bacterial polysaccharides were discussed in Sections 7.9 and 7.10. Specific pyrolysis products such as propionamide or peaks characteristic for KDO have been used for Py-MS or Py-GC/MS characterization of microorganisms. 

Critical amounts of cortex (a peptidoglycan layer of bacterial spores) are required for different properties of Bacillus sphaericus spores. Characteristic properties of the spores, such as the refractility and the resistance to xylene, octanol, and heat, were measured. Reduction with sodium borotritide and acid hydrolysis, etc., has been used to detect muramic lactam, which is located specifically in the cortical peptidoglycan of bacterial spores. The cortex content of several sporulation-deficient mutants of B. subtilis was examined using this procedure. 

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