vsv5

930 views
877 views

Published on

Published in: Technology, Business
0 Comments
1 Like
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total views
930
On SlideShare
0
From Embeds
0
Number of Embeds
0
Actions
Shares
0
Downloads
14
Comments
0
Likes
1
Embeds 0
No embeds

No notes for slide

vsv5

  1. 1. Dr. Alvin Fox Antibiotics affecting the cell envelope
  2. 2. 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
  3. 3. STERILIZATION <ul><li>All killed </li></ul><ul><li>non-selective </li></ul>
  4. 4. Sterilization <ul><li>autoclaving </li></ul><ul><ul><li>121 o C (heat/pressure) </li></ul></ul><ul><ul><ul><ul><li>Heat resistant materials </li></ul></ul></ul></ul><ul><li>ethylene oxide </li></ul><ul><ul><li>non heat resistant </li></ul></ul><ul><ul><li>Usually equipment </li></ul></ul><ul><ul><li>being replaced e.g. H 2 O 2 /free radicals </li></ul></ul><ul><li>ultra-violet light </li></ul><ul><ul><li>surfaces (e.g operating rooms) </li></ul></ul><ul><ul><li>not totally effective </li></ul></ul><ul><li>gamma radiation </li></ul><ul><ul><li>food </li></ul></ul><ul><ul><li>some mail </li></ul></ul>
  5. 5. Membrane filters pores bacteria
  6. 6. Disinfection <ul><li>Liquids that kill bacteria </li></ul><ul><ul><li>e.g. phenol based </li></ul></ul><ul><ul><li>too toxic for skin surfaces </li></ul></ul>
  7. 7. Antiseptics <ul><li>Topical (e.g. skin) </li></ul><ul><ul><li>e.g. iodine or 70% alcohol </li></ul></ul><ul><ul><li>“ reduce” bacterial load </li></ul></ul>
  8. 8. ANTIBIOTICS <ul><li>Selectively toxic for bacteria </li></ul><ul><ul><li>bactericidal (killing) </li></ul></ul><ul><ul><li>bacteriostatic (growth inhibition) </li></ul></ul><ul><li>no harm to patient </li></ul>
  9. 9. Antibiotics <ul><li>destroy structures </li></ul><ul><ul><li>present in bacteria </li></ul></ul><ul><ul><li>not present in host </li></ul></ul>
  10. 10. Antibiotics work together with immune system
  11. 11. Minimal inhibitory concentration <ul><li>lowest level stopping growth </li></ul><ul><li>e. g. zone of inhibition around a disk impregnated with antibiotic </li></ul>
  12. 12. <ul><li>Antibiotics that inhibit cell wall </li></ul><ul><li>biosynthesis are bactericidal </li></ul><ul><li>Without cell wall, osmotic pressure </li></ul><ul><li>causes bacteria to burst </li></ul>
  13. 13. Cross-linking of peptidoglycan Old New
  14. 14. Peptidoglycan synthesis Cytoplasm Cell wall undecaprenol sugar amino acid Cell Membrane
  15. 15. Cycloserine <ul><ul><li>alanine (ala) analog </li></ul></ul><ul><ul><li>inhibits conversion of L-ala to D-ala </li></ul></ul><ul><ul><li>inhibits formation of D-ala-D-ala </li></ul></ul>
  16. 16. Cycloserine Analog of alanine X Cytoplasm sugar amino acid X X X
  17. 17. Bacitracin <ul><li>Inhibits dephosphorylation </li></ul>
  18. 18. TRANSPORT OF PEPTIGOGLYCAN SUBUNIT ACROSS MEMBRANE Cell membrane undecaprenol P P Cell wall
  19. 19. TRANSPORT OF PEPTIGOGLYCAN SUBUNIT ACROSS MEMBRANE Cell membrane undecaprenol P Cell wall P
  20. 20. TRANSPORT OF PEPTIGOGLYCAN SUBUNIT ACROSS MEMBRANE Cell membrane undecaprenol P P Cell wall
  21. 21. TRANSPORT OF PEPTIGOGLYCAN SUBUNIT ACROSS MEMBRANE Cell membrane undecaprenol P P Cell wall
  22. 22. TRANSPORT OF PEPTIGOGLYCAN SUBUNIT ACROSS MEMBRANE Cell membrane undecaprenol P P Cell wall
  23. 23. MINUS BACITRACIN Cell membrane undecaprenol P Cell wall TRANSPORT OF PEPTIGOGLYCAN SUBUNIT ACROSS MEMBRANE
  24. 24. PLUS Bacitracin Cell membrane undecaprenol P P Cell wall TRANSPORT OF PEPTIGOGLYCAN SUBUNIT ACROSS MEMBRANE
  25. 25. Vancomycin Cell wall <ul><li>binds to D-ala-D-ala </li></ul><ul><li>inhibits cross-linking </li></ul>Vancomycin
  26. 26. Beta lactam antibiotics <ul><li>penicillins </li></ul><ul><li>Cephalosporins/cephamycins </li></ul><ul><li>monobactams </li></ul>
  27. 27. Beta lactams Cell wall Penicillin binding protein <ul><li>inhibit penicillin binding proteins </li></ul><ul><li>stop cross-linking </li></ul>Beta lactam
  28. 28. 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
  29. 29. Attached to lactam ring <ul><li>penicillins </li></ul><ul><ul><li>5 membered ring </li></ul></ul><ul><li>Cephalosporins/cephamycins </li></ul><ul><ul><li>6 membered ring </li></ul></ul><ul><li>monobactams </li></ul><ul><ul><li>no second ring </li></ul></ul>
  30. 30. Chemical modifications change biological activity <ul><li>Early lactam antibiotics </li></ul><ul><ul><li>inactive against Gram negative bacteria </li></ul></ul><ul><li>no penetration of outer membrane </li></ul>
  31. 31. Resistance mechansims <ul><li>Produce beta lactamase (penicillinase) </li></ul><ul><ul><li>destroys antibiotic </li></ul></ul><ul><li>modified penicillin binding proteins </li></ul><ul><ul><li>don’t bind antibiotic </li></ul></ul><ul><li>modified porins </li></ul><ul><ul><li>no internalization of antibiotic </li></ul></ul>
  32. 32. <ul><li>beta lactam </li></ul><ul><li>binds strongly beta lactamases </li></ul><ul><ul><li>inhibits activity </li></ul></ul>Clavulinic acid
  33. 33. Polymyxin B <ul><li>binds </li></ul><ul><ul><li>lipid A </li></ul></ul><ul><ul><li>phospholipids </li></ul></ul><ul><li>disrupts outer membrane, Gram negative bacteria </li></ul><ul><li>toxic to human cells </li></ul>
  34. 34. Isoniazid, Ethambutol, Ethionamide   Isoniazid and Ethionamide - chemically related - blocks mycolic acid synthesis Ethambutol - blocks arabinogalactan synthesis Anti-tuberculosis drugs

×