Thursday,

24 October 2019 1:12 PM

The cell walls of bacteria

® are essential for their normal growth and development.

○ Peptidoglycan
® is a heteropolymeric component of the cell wall that provides rigid mechanical stability by virtue of its
highly cross-linked latticework structure (Figure 53–2).

} In grampositive microorganisms
w the cell wall is 50-100 molecules thick,

} In gram negative microorganism it is only 1 or 2 molecules thick

® The peptidoglycan is composed of glycan chains

w which are linear strands of two alternating amino sugars: (N-
acetylglucosamine and N-acetylmuramic acid) that are cross-
linked by peptide chains.

BASIC MICROBIOLOGY: formation of cell wall

Mechanism of Action:

The biosynthesis of the peptidoglycan involves ~30 bacterial enzymes and may be considered in three stages.
1) The first stage: precursor formation
w takes place in the cytoplasm
w The product, uridine diphosphate (UDP)–acetylmuramyl-pentapeptide, accumulates in cells when subsequent
synthetic stages are inhibited.

w The last reaction in the synthesis of this compound is the addition of a dipeptide, D-alanyl-Dalanine.( See
figure)

w Synthesis of the dipeptide involves prior racemization of L-alanine and condensation catalyzed by D-alanyl-D-
alanine synthase. D-Cycloserine is a structural analog of D-alanine and acts as a competitive inhibitor of both the
racemase and the synthase (Chapter 56).

2) second stage, UDP-acetylmuramylpentapeptide and UDP-acetylglucosamine are linked (with the release of the uridine nucleotides)
to form a long polymer.

3) The third and final stage

w involves completion of the cross-link.
w This is accomplished by peptidoglycan glycosyltransferases outside the cell membrane of gram-positive and within
the periplasmic space of gram-negative bacteria

® The terminal glycine residue of the pentaglycine bridge is linked to the fourth residue of the pentapeptide (D-alanine), releasing
the fifth residue (also D-alanine)

It is this last step in peptidoglycan synthesis that is inhibited by the β-lactam antibiotics and glycopeptide antibiotics such as
vancomycin.

SUMMARY OF MECHANISM OF ACTION: Penicillin/ Cephalosporins