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Antibiotics that affect the Cell Envelope

Antibiotics that affect the Cell Envelope. Key Words. Sterilization/disinfection/antisepsis Bacitracin Antibiotic Vancomycin Selective toxicity beta lactam

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Antibiotics that affect the Cell Envelope

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  1. Antibiotics that affect the Cell Envelope

  2. Key Words Sterilization/disinfection/antisepsis Bacitracin Antibiotic Vancomycin Selective toxicity beta lactam Bactericidal Penicillins Bacteriostatic Cephalosporins Minimal inhibitory concentration (MIC) Monobactam Susceptibility testing Clavulinic acid Penicillin binding proteins Penicillinase/beta lactamase Autolysins Polymyxin B Cycloserine Resistance

  3. STERILIZATION • All killed • non-selective

  4. Sterilization • autoclaving • 121oC (heat/pressure) • Heat resistant materials • ethylene oxide • Non heat resistant • usually equipment • ultra-violet light • surfaces (e.g operating rooms) • not totally effective

  5. Membrane filters pores bacteria

  6. Disinfection • Liquids that kill bacteria • e.g. phenol based • too toxic for skin surfaces

  7. Antiseptics • Topical (e.g. skin) • e.g. iodine or 70% alcohol • “reduce” bacterial load

  8. ANTIBIOTICS • Selectively toxic for bacteria • bactericidal (killing) • bacteriostatic (growth inhibition) • no harm to patient

  9. Antibiotics • destroy structures • present in bacteria • not present in host

  10. Antibiotics work together with immune system

  11. Minimal inhibitory concentration • lowest level stopping growth • e. g. zone of inhibition around a disk impregnated with antibiotic

  12. Antibiotics that inhibit cell wall • biosynthesis are bactericidal • Without cell wall, osmotic pressure • causes bacteria to burst

  13. Peptidoglycan synthesis Cell Membrane Cytoplasm Cell wall undecaprenol sugar amino acid

  14. Cycloserine • alanine (ala) analog • inhibits conversion of L-ala to D-ala • inhibits formation of D-ala-D-ala

  15. Cycloserine Analog of alanine Cytoplasm X X sugar amino acid X X

  16. Bacitracin • Inhibits dephosphorylation

  17. Bacitracin Cell membrane undecaprenol P P

  18. Vancomycin • binds to D-ala-D-ala • inhibits cross-linking

  19. Vancomycin Cell wall

  20. Beta lactam antibiotics • penicillins • cephalosporins • monobactams • inhibit penicillin binding proteins • stop cross-linking

  21. Beta lactams Cell wall Penicillin binding protein

  22. Cross-linking of peptidoglycan

  23. O S CH3 C NH CH C CH CH3 O C N CH COOH STRUCTURE OF PENICILLIN Site of penicillinase action. Breakage of the  lactam ring.

  24. Attached to lactam ring • penicillins • 5 membered ring • cephalosporins • 6 membered ring • monobactams • no second ring

  25. Chemical modifications change biological activity • Early lactam antibiotics • inactive against Gram negative bacteria • no penetration of outer membrane

  26. Resistance mechansims • Produce beta lactamase (penicillinase) • destroys antibiotic • modified penicillin binding proteins • don’t bind antibiotic • modified porins • no internalization of antibiotic

  27. Clavulinic acid • beta lactam • binds strongly beta lactamases • inhibits activity

  28. Polymyxin B • binds • lipid A • phospholipids • disrupts outer membrane, Gram negative bacteria • toxic to human cells

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