The Beta-Lactams

The Beta-Lactams




The beta-lactams get their name from the characteristic ring structure — shown here in blue
— that they all share. (The green arrow shows the bond that is broken by the beta-lactamases that are synthesized by many penicillin-resistant bacteria.)


They include the

• penicillins such as
  
  
  
  • penicillin G (a natural product) produced by the fungus Penicillium chrysogenum
    
  • ampicillin (a semi-synthetic)
    
  • amoxicillin (semi-synthetic)
    
  
  
  


• cephalosporins
  There are over two dozen of them in current use. Most are
  semi-synthetics derived from the secretion of the mold Cephalosporium.
  Some examples:
  
  
  
  • cephalexin (e.g., Keflex)
    
  • cefaclor (e.g., Ceclor)
    
  • cefixime (e.g., Suprax)
    
  
  


• carbapenems such as
  
  
  
  • meropenem (Merrem)
    
  • ertapenem (Invanz)
    

The Chink in the Armor = the bacterial cell wall



The
beta-lactams all work by interfering with the synthesis of the
bacterial cell wall — a structure that is not found in eukaryotes.
The walls of bacteria are made of a complex polymeric material called peptidoglycan. It contains both amino acids and amino sugars.
The amino sugars are of two kinds

• N-acetylglucosamine (NAG) and its close relative
  
• N-acetylmuramic acid (NAM).
  

These two form a linear polymer of NAG alternating with NAM. They are linked by a glycosidic bond between the #1 and #4 carbons (this is the linkage attacked by lysozyme) and are oriented in the same way they are in cellulose.
Side chains containing 4 or 5 amino acids are attached to each NAM.
These form covalent bonds with amino acids in adjacent chains. The
bonds may

• be direct to the next chain or
  
• include additional peptide cross bridges (e.g., 5 glycine residues) which
  
• extend to chains in the same plane (shown here) as well as to chains above and below.
  

This elaborate, covalently
cross-linked structure provides the great strength of the cell wall. It
also leads to the remarkable conclusion that the bacterial cell wall
meets the definition of a single molecule!

The beta-lactam antibiotics bind to and inhibit enzymes needed for
the synthesis of the peptidoglycan wall. While they have little effect
on resting bacteria, they are lethal to dividing bacteria as defective
walls cannot protect the organism form bursting in hypotonic surroundings.