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1 Bacterial cell envelope and antibiotics efficacy 2 The Cell Membrane (1) selective permeability and transport of solutes (2) electron transport and oxidative phosphorylation in aerobic species (3) excretion of hydrolytic exoenzymes (4) bearing the enzymes and carrier molecules that function in the biosynthesis of DNA, cell wall polymers, and membrane lipids (5) bearing the receptors and other proteins of the chemotactic and other sensory transduction systems 3 Permeability and transport uniport Active transport Ion-coupled transport symport ABC transport antiport Simple diffusion transports Passive transport Facilitated diffusion Group translocation Vectorial metabolism Special transport processes Fe transport Channel proteins 4 Group translocation 5 Excretion of hydrolytic exoenzymes and pathogenicity proteins 6 Excretion of hydrolytic exoenzymes and pathogenicity proteins α-hemolysin E coli adenylyl cyclase Bordetella pertussis Type l Elastase Type ll phospholipase C Pseudomonas aeruginosa exotoxin A Excretion protein Type lll Type lV protein–DNA complexes Agrobacterium tumefaciens pertussis toxin B pertussis interleukin-8–inducing factor H pylori IgA protease Neisseria gonorrhoeae vacuolating cytotoxin Helicobacter pylori Type V 7 Special Components of Gram-Negative and Gram- positive Cell Walls Gram-negative: Gram-positive: 1. Outer membrane 1.Teichoic acid 2. Lipopolysaccharide (LPS) 2.Lipoteichoic acid 3.Lipoprotein 3.Teichoronic acid 4.The periplasmic space 8 Special Components of Gram-Positive Cell Walls 9 Special Components of Gram-Negative Cell Walls 10 The Peptidoglycan Layer 11 Biosynthetic functions : Synthesis of Cell Wall Peptidoglycan 12 D-Ala-D-Ala synthesis 13 INHIBITION OF CELL WALL SYNTHESIS penicillin's cephalosporin's β-lactam drugs monobactams carpabenem antibiotics glycopeptide Vancomycin other Cycloserine 14 The mimicry of beta-lactam antibiotics to acyl-D-alanyl-D-alanine (D-Ala-D-Ala) 15 Mechanism of action β-lactam 16 The model of beta-lactamase induction in Gram-negative bacteria 17 Beta-lactamase 18 vancomycin 19 cycloserine is an amino acid derivative with an unusual structure As a cyclic analogue of Dalanine, cycloserine acts against two crucial enzymes important in the cytosolic stages of peptidoglycan synthesis: alanine racemase (Alr) and D-alanine:Dalanine ligase (Ddl) 20 Bacitracin 21 Lysozyme 22 INHIBITION/ALTERATION OF CELL MEMBRANE FUNCTION detergent-like • Polymyxins permit rapid diffusion of specific cations through the membrane • Daptomycin specifically interfere with biosynthetic functions of the cytoplasmic membranes • Novobiocin 23 Polymyxins 24 Daptomycin 25 Antimicrobial peptides are part of the innate immune response found among all classes of life These peptides are potent, broad spectrum antibiotics Are cationic and bind to acidic bacterial membrane 26 AMPs mechanism of action 27