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    vsv5 vsv5 Presentation Transcript

    • Dr. Alvin Fox Antibiotics affecting the cell envelope
    • Key Words Sterilization/disinfection/antisepsis Vancomycin Antibiotic beta lactam Selective toxicity Penicillins Bactericidal Cephalosporins/cephamycins Bacteriostatic Monobactam Minimal inhibitory concentration (MIC) Clavulinic acid Susceptibility testing Polymyxin B Penicillin binding proteins Isoniazid Penicillinase/beta lactamase Ethioniamide Autolysins Ethambutol Cycloserine Resistance Bacitracin
    • STERILIZATION
      • All killed
      • non-selective
    • Sterilization
      • autoclaving
        • 121 o C (heat/pressure)
            • Heat resistant materials
      • ethylene oxide
        • non heat resistant
        • Usually equipment
        • being replaced e.g. H 2 O 2 /free radicals
      • ultra-violet light
        • surfaces (e.g operating rooms)
        • not totally effective
      • gamma radiation
        • food
        • some mail
    • Membrane filters pores bacteria
    • Disinfection
      • Liquids that kill bacteria
        • e.g. phenol based
        • too toxic for skin surfaces
    • Antiseptics
      • Topical (e.g. skin)
        • e.g. iodine or 70% alcohol
        • “ reduce” bacterial load
    • ANTIBIOTICS
      • Selectively toxic for bacteria
        • bactericidal (killing)
        • bacteriostatic (growth inhibition)
      • no harm to patient
    • Antibiotics
      • destroy structures
        • present in bacteria
        • not present in host
    • Antibiotics work together with immune system
    • Minimal inhibitory concentration
      • lowest level stopping growth
      • e. g. zone of inhibition around a disk impregnated with antibiotic
      • Antibiotics that inhibit cell wall
      • biosynthesis are bactericidal
      • Without cell wall, osmotic pressure
      • causes bacteria to burst
    • Cross-linking of peptidoglycan Old New
    • Peptidoglycan synthesis Cytoplasm Cell wall undecaprenol sugar amino acid Cell Membrane
    • Cycloserine
        • alanine (ala) analog
        • inhibits conversion of L-ala to D-ala
        • inhibits formation of D-ala-D-ala
    • Cycloserine Analog of alanine X Cytoplasm sugar amino acid X X X
    • Bacitracin
      • Inhibits dephosphorylation
    • TRANSPORT OF PEPTIGOGLYCAN SUBUNIT ACROSS MEMBRANE Cell membrane undecaprenol P P Cell wall
    • TRANSPORT OF PEPTIGOGLYCAN SUBUNIT ACROSS MEMBRANE Cell membrane undecaprenol P Cell wall P
    • TRANSPORT OF PEPTIGOGLYCAN SUBUNIT ACROSS MEMBRANE Cell membrane undecaprenol P P Cell wall
    • TRANSPORT OF PEPTIGOGLYCAN SUBUNIT ACROSS MEMBRANE Cell membrane undecaprenol P P Cell wall
    • TRANSPORT OF PEPTIGOGLYCAN SUBUNIT ACROSS MEMBRANE Cell membrane undecaprenol P P Cell wall
    • MINUS BACITRACIN Cell membrane undecaprenol P Cell wall TRANSPORT OF PEPTIGOGLYCAN SUBUNIT ACROSS MEMBRANE
    • PLUS Bacitracin Cell membrane undecaprenol P P Cell wall TRANSPORT OF PEPTIGOGLYCAN SUBUNIT ACROSS MEMBRANE
    • Vancomycin Cell wall
      • binds to D-ala-D-ala
      • inhibits cross-linking
      Vancomycin
    • Beta lactam antibiotics
      • penicillins
      • Cephalosporins/cephamycins
      • monobactams
    • Beta lactams Cell wall Penicillin binding protein
      • inhibit penicillin binding proteins
      • stop cross-linking
      Beta lactam
    • Site of penicillinase action. Breakage of the  lactam ring. STRUCTURE OF PENICILLIN C NH CH CH C O O C N CH CH 3 CH 3 COOH S
    • Attached to lactam ring
      • penicillins
        • 5 membered ring
      • Cephalosporins/cephamycins
        • 6 membered ring
      • monobactams
        • no second ring
    • Chemical modifications change biological activity
      • Early lactam antibiotics
        • inactive against Gram negative bacteria
      • no penetration of outer membrane
    • Resistance mechansims
      • Produce beta lactamase (penicillinase)
        • destroys antibiotic
      • modified penicillin binding proteins
        • don’t bind antibiotic
      • modified porins
        • no internalization of antibiotic
      • beta lactam
      • binds strongly beta lactamases
        • inhibits activity
      Clavulinic acid
    • Polymyxin B
      • binds
        • lipid A
        • phospholipids
      • disrupts outer membrane, Gram negative bacteria
      • toxic to human cells
    • Isoniazid, Ethambutol, Ethionamide   Isoniazid and Ethionamide - chemically related - blocks mycolic acid synthesis Ethambutol - blocks arabinogalactan synthesis Anti-tuberculosis drugs