Antibiotics and inhibition of cell wall in bacteria

• The cell wall is a component of most microorganisms.

• All cell walls contain a rigid components.

• Several antibiotics are known to inhibit the biosynthesis of cell wall polymers in bacteria and fungi.

Bacterial Cell wall

Composition and of cell wall

• Macromolecular components of cell wall:

- Peptidoglycan- Lipopolysaccharides- Lipoproteins- Proteins- Polysaccharides

Peptidoglycan as heteropolymers

1- Aminopolysaccharides: - Alternative N- acetylglucosamine GLU-NAC and N-acetylmuramic acid Mur NAC2- Amino acids: - L- alanine - D-glutamic - meso- diaminopimelic acid or L diaminopemilic acid - L- lysine - D-alanine

Gram negative bacteria

Gram positive bacteria

• In gram +ve bacteria e.g Staphylococcus aureus all peptide chains are joined together through pentaglycin bridges and diaminopimelic acid is substituted by L-lysine.

Synthesis of cell wall

Penicillins

• In the presence of penicillins, bacterial cell undergoes a change to spherical form i.e it interferes with cell wall biosynthesis.

• Penicillin inhibits the last step inpeptidoglycan bisynthesis (i.e transpeptidation).

Mechanism of cell wall synthesis inhibition

• a- Penicillin may competitively inhibits transpeptidase.

• Inhibits transpeptidation by binding to the substrate at the free NH2 group of pentaglycin and preventing the formation of the peptide bond in the cross-linking reaction. (penicillin binds through its COOH group.

Antibiotics inhibiting bacterial cell wall

• This could be due to:

a- Inhibition of one or more of the biosynthetic enzymes. Phosphonomycin, cycloserine and penicillin.

b- Bind to the lipid carrier in the membrane e.g bacitracin.

c-Complex with the growing point of peptidoglycans. e.g. Vanomycin

• D- cycloserine is antagonist of D-alanine. If it present in media, bacteria transformed into spheroplasts.

• It inhibits the utilization of D-alanine in cell wall synthesis.

• But experimentally, bacterial growth could be restored by the addition of D-alanine.

Cycloserine

Phosphonomycin

• It is a broad spectrum antibiotic.• It inhibits the synthesis of cell wall through

inhibiting the synthesis of MUR-NAC from UDP-Glc-NAC + PEP (Phosphoenolpyruvate).

• http://www.microbelibrary.org/images/spencer/spencer_cellwall.html

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