复旦大学：《医学微生物学 Medical Microbiology（MBBS）》课程讲义_理论课_Lecture2-penicilin target

The Cell wall Peptidoglycan Staphylococcus aureus peptidoglycan D-nlutame Dante D More than 40 sheets in Gram positive bacteria E coli peptidoglycan Only 1-2 sheets n Gram negative bacteria

Peptidoglycan More than 40 sheets in Gram positive bacteria Only 1-2 sheets In Gram negative bacteria The Cell Wall

Gram* Peptidoglycan N-acetylglucosamine(NAG) Tetrapeptide side chain 0 N-acetylmuramic acid(NAM) Peptide cross-bridge Side chain amino acid O cross-bridge amino acid NAM Peptide bond NAG Carbohydrate backbone (a)Structure of peptidoglycan in gram-positive bacteria opyright e 2004 Pearson Education, Inc publishing as Ben amin Cummi

Gram+ Peptidoglycan 2

The Cell wall Outside Peptidoglycan synthesis Peptidoglycan grow int of cell wall M-G-M-G-M-G-M-G-M-G-M-G-M-G-M-G-M-G M一G-M一G-M-G-M一G-M一G-M一G M一G-M一G -M-G ntapeptide Cytoplasmic membrane M一G一 Bacitracin Bact Inside Bactoprenol phosphate transports Nam and nag across the cell membrane in the synthesis of peptidoglycan Figure 6-19 p88

Bactoprenol phosphate transports NAM and NAG across the cell membrane in the synthesis of peptidoglycan Figure 6-19 p.88 Peptidoglycan synthesis The Cell Wall Bacitracin

synthesis of cell UDP- NAG) and UDP(NAM wall precursors Peptidoglycan cyclosarin inhibits reactions involved synthesis and in incorporation of alanine into cell wall precursor antibiotics cytoplasmic membrane synthesis of new cel NAG NAM wall subunit attached to bacitracin prevents dephospho phospholipid which prevents rege bind to terminal of camier necessary for D-ala-D-ala residues ● synthesis tu Continu prevent incorporation of subunit into cell wall attachment of new NAG)。.KNAM。、(NAG0〈NAM0、(NAG)0 wall unit to ●△ △ beta-lactams enzvmes which

Peptidoglycan synthesis and antibiotics

Side chain: General structure of penicillin Ampicillin Be Cloxacillin CH Phenoxymethyl- Ticarcillin H B-lactam drugs β4 actam COoH B-lactamase(penicillinase) Peptide- glycan matrⅸ Penicillin-binding protein Rigid cell wall of Gram-positive bacteria 口β lactam drugs Lipopolysacch aride lay el Th in matrⅸ Penicillin-bindin g protein Gram-negative bacterial wall Fig 33-1 KMc

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Cell survival Cell survival No transport across Drug hydrolyzed Cell wall outer membrane pre cursors Penicillin-binding Environment >Outer Periplasmic proteins(PBPs) space membrane ↓ catalyze synthesis e.g. transpeptidases β- actam antibiotic Binds carboxy peptidases PBPs endopeptidases peptidoglycan Cell death B-lactam antibiotic Falls to blind Mutant PBPsCell survival GRAM-NEGATIVE BACTERIA

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Penicillin rupture later Bacterium owww.scienceaidco.uk

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Lys-type peptidoglycan (group A3) DAP-type peptidoglycan(mDpm-dlirect) PGRP-LC recognition structure G PGRP-SA recognition structure G: GICNAC M: MurNAc Gt Peptidoglycan G- Peptidoglycan Peptidoglycan recognition protein, PGRP

G+ Peptidoglycan G- Peptidoglycan Peptidoglycan recognition protein, PGRP 8