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Antibiotics and inhibition of cell wall in bacteria
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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
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Composition and of cell wall Macromolecular components of cell wall: -Peptidoglycan -Lipopolysaccharides -Lipoproteins -Proteins -Polysaccharides
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Peptidoglycan as heteropolymers 1- Aminopolysaccharides: - Alternative N- acetylglucosamine GLU-NAC and N-acetylmuramic acid Mur NAC 2- Amino acids: - L- alanine - D-glutamic - meso- diaminopimelic acid or L diaminopemilic acid - L- lysine - D-alanine
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Gram negative bacteria
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Gram positive bacteria
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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.
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Synthesis of cell wall
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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).
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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.
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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
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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
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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).
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http://www.microbelibrary.org/images/spenc er/spencer_cellwall.html Enjoy watching the animated lecture through this link
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