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BIO370Y5 (13)

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Tim Westwood

Cell Structure: Bacterial and Archaeal Cell Envelopes Action of Antibiotics Penicillin Other inhibitors of cell wall synthesis Antibiotic Resistance Gram-positive Cell Wall Teichoic acid Structure Cell Walls of the Archaea Pseudopeptidoglycan Halococcus & Others Outer Membrane of Gram-negative Bacteria Prescott 8th ed: Chapter 3 pages 57-58 and 63-65; Chapter 18 pages 473-477 Degradation of peptidoglycan A number of enzymes known to cause the decomposition Lysozyme - Breaks -1,4 glycosidic bonds (product monosaccharides) Muramidase - Breaks -1,4 glycosidic bonds (product disaccharides) Autolysins - Hydrolyze transpeptide bonds Penicillin - prevents synthesis of peptidoglycan Penicillin: General Structure A -lactam antibiotic Penicillin first discovered by Ernest Duchesne (1896), but discovery lost accidentally discovered by Alexander Fleming (1928) observed penicillin activity on contaminated plate did not think could be developed further effectiveness demonstrated by Florey, Chain, and Heatley (1939) Fleming, Florey and Chain received Nobel Prize in 1945 for discovery and production of penicillin Figure 34.1 Penicillins- inhibit peptidoglycan synthesis Penicillinase - enzyme produced by penicillin resistant bacteria Figure 34.5 Natural & Semi-synthetic Penicillins Narrow & Broad Spectrum The -lactam region of the drug resembles the D-Ala-D-Ala end of the peptide to which the transpeptidase enzyme binds. The structures are shown below. How does penicillin work to kill bacterial cells ? Mechanism of Inhibition of PBPs Much more effective against PBP1A, 1B & 2 than PBP4 !
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