1. Microbiology: A Systems Approach
PowerPoint to accompany
Microbiology: A Systems Approach
Cowan/Talaro
Chapter 12
Drugs, Microbes, Host- The Elements of Chemotherapy
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2. Chapter 12 Topics - Antimicrobial Therapy - Selective Toxicity
- Survey of Antimicrobial Drug
- Microbial Drug Resistance
- Drug and Host Interaction

3. Antimicrobial Therapy
Ideal drug
Terminology
Antibiotics

4. Important characteristics regarding antimicrobial drugs.
Table 12.1 Characteristics of the ideal antimicrobial drug

5. Important terms related to chemotherapy.
Table 12.2 Terminology of chemotherapy

6. Antibiotics Naturally occurring antimicrobials Bacteria Molds
Metabolic products of bacteria and fungi
Reduce competition for nutrients and space
Bacteria
Streptomyces, Bacillus,
Molds
Penicillium, Cephalosporium

7. Selective Toxicity
Drugs that specifically target microbial processes, and not the human host cellular processes.

8. Selective Toxicity Mechanism of action Bacterial cell wall
Nucleic acid synthesis
Protein synthesis
Cell membrane
Folic acid synthesis

9. The mechanism of action for different antimicrobial drug targets in bacterial cells.
Fig Primary sites of action of antimicrobial drugs
on bacterial cells.

10. Cell wall synthesis Bactericidal
Cycloserine – inhibits the formation of the basic peptidoglycan subunits
Vancomycin – hinders peptidoglycan elongation
Penicillin and cephalosporins – binds and blocks peptidases involved in cross-linking the glycan molecules

11. Antibiotics weaken the cell wall, and cause the cell to lyse.
Fig The consequences of exposing a growing cell to antibiotics that prevent cell wall synthesis.

12. The mechanism of cell wall inhibition by penicillins and cephalosporins.
Fig The mode of action of penicillins and cephalosporins

13. Nucleic acid synthesis
Chloroquine – binds and cross-links the double helix
Other quinolones – inhibits DNA unwinding enzymes
Viruses
Asidothymidine (AZT)
Analogs of purines and pyrimidines

14. Protein synthesis Aminoglycosides Tetracyclines Chloramphenicol
Binds the 30S ribosome
Misreads mRNA
Tetracyclines
Blocks attachment of tRNA
Chloramphenicol
Binds to the 50S ribosome
Prevents peptide bond formation

15. Examples of different antibiotics and their sites of inhibition on the procaryotic ribosome.
Fig Sites of inhibition on the procaryotic ribosome
and major antibiotic that act on these sites.

16. Cell membrane Polymyxins Anit-fungal
Interact with membrane phospholipids
Distorts the cell surface
Leakage of proteins and nitrogen bases
Anit-fungal
Amphoterin B
Forms complexes with sterols in the membrane
Leakage
Can affect human cell membranes (toxicity)

17. Folic acid synthesis Sulfonamides (sulfa drug) and trimethoprim
Analogs
Competitive inhibition
Prevents the metabolism of DNA, RNA, and amino acid

18. Sulfonamides compete with PABA for the active site on the enzyme.
Fig The mode of action of sulfa drug.

19. Survey of Antimicrobial Drugs
Penicillin
Cephalosporins
Streptomycin
Tetracyline
Sulfomides
Polyenes
Antiviral

20. Important chemotherapeutic agents used to treat infectious diseases.
Table 12.3 Selected survey o chemotherapeutic agents
in infectious diseases.

21. Important chemotherapeutic agents used to treat infectious diseases.
Table 12.3 Selected survey o chemotherapeutic agents
in infectious diseases.

22. Important chemotherapeutic agents used to treat infectious diseases.
Table 12.3 Selected survey o chemotherapeutic agents
in infectious diseases.

23. Penicillin Penicillin chrysogenum
A diverse group (1st, 2nd , 3rd generations)
Natural (penicillin G and V)
Semisynthetic (ampicillin)
Structure
Thiazolidine ring
Beta-lactam ring
Variable side chain (R group)

24. Penicillin continued Resistance – if bacteria contain penicillinases
Inhibits cell wall synthesis
Treat streptococci, meningococci, and spirochete infections

25. The R group is responsible for the activity of the drug, and cleavage of the beta-lactam ring will render the drug inactive.
Fig Chemical structure of penicillins

26. Cephalosporin Cephalosporium acremonium (mold)
Widely administered today
Diverse group (natural and semisynthetic)
Structure
similar to penicillin except
Main ring is different
Two sites for R groups

27. Cephalosporin continued
Resistant to most pencillinases
Broad-spectrum – inhibits cell wall synthesis
3rd generation drugs used to treat enteric bacteria, respiratory, skin, urinary and nervous system infections

28. The different R groups allow for versatility and improved effectiveness.
Fig The structure of cephalosporins

29. Aminoglycosides Streptomyces and Micromonospora Structure
Amino sugars and an aminocyclitol ring
Broad-spectrum
Commonly used to treat bubonic plague and sexually transmitted diseases
Inhibits protein synthesis

30. The amino sugars and six-carbon ring (aminocyclitol) are characteristics associated with streptomycin.
Fig The structure of streptomycin

31. Streptomyces synthesizes many different antibiotics such as aminoglycosides, tetracycline, chloramphenicol, and erythromycin.
Fig A colony of Streptomyces

32. Tetracycline Streptomyces Structure – Broad spectrum and low cost
Diverse
complex series of rings
Broad spectrum and low cost
Commonly used to treat sexually transmitted diseases
Side effects – gastrointestinal disruption
Inhibits proteins synthesis

33. Chloramphenicol Streptomyces Structure - nitrobenzene structure
Broad-spectrum
Only made synthetically today
Treat typhoid fever, brain abscesses
Side effects – aplastic anemia
Inhibits protein synthesis

34. Erythromycin Streptomyces Structure – macrolide ring Broad-spectrum
Commonly used as prophylactic drug prior to surgery
Side effects - low toxicity
Inhibits protein synthesis

35. Comparison of three broad-spectrum antibiotics tetracycline, chloramphenicol, and erythromycin.
Fig Structures of three broad-spectrum antibiotics

36. Sulfonamides (sulfa drugs)
Synthetic drug
Based on sulfanilamides
Used in combination with other synthetics such as trimethoprim
Commonly used to treat pneumonia in AIDS patients
Inhibits folic acid synthesis

37. Attachment of different R groups to the main structural nucleus enables versatility of sulfonamides.
Fig The structures of some sulfonamides

38. Polyenes Antifungal Structure – large complex steroidal structure
Some toxicity to humans
Commonly used for skin infections
Targets the membrane - lost of selective permeability

39. Comparison of different antifungal drug structures, which include polyenes, azoles, and flucytosine.
Fig Some antifungal drug structures

40. Other types of antimicrobials
Antiprotozoan – metronidazole
Treat giardia
Antimalarial – Quinine
malaria
Antihelminthic – mebendazole
Tapeworms, roundworms

41. Antiviral Limited drugs available
Difficult to maintain selective toxicity
Effective drugs – target viral replication cycle
Entry
Nucleic acid synthesis
Assembly/release
Interferon – artificial antiviral drug

42. Antiviral drug structures and their mode of action.
Table 12.5 Actions of selected antiviral drugs.

43. Antiviral drug structures and their mode of action.
Table 12.5 Actions of selected antiviral drugs.

44. Antiviral drug structures and their mode of action.
Table 12.5 Actions of selected antiviral drugs.

45. Antimicrobial Resistance
Resistance factors
New enzymes
Permeability
Alter receptors
Change metabolic patterns
Natural selection
New approaches

46. Intermicrobial transfer of plasmids containing resistance genes (R factors) occurs by conjugation, transformation,and transduction.
Fig Spread of resistance factors

47. Different mechanisms that are commonly associated with drug resistance.
Fig Examples of mechanisms of acquired drug resistance

48. Demonstration of how natural selection enables resistant strains to become dominant.
Fig The events in natural selection for drug resistance

49. New approaches
Increase drug resistance requires new approaches for developing effective antimicrobials
Prevent iron –scavenging capabilities
Inhibit genetic controls (riboswitches)
Probiotics and prebiotics

50. Drug and Host Interaction
Toxicity to organs
Allergic reactions
Suppress/alter microflora
Effective drugs

51. Tetracycline treatments can cause teeth discoloration.
Fig Drug-induced side effect.

52. Disrupting the microflora in the intestine can result in superinfections.
Fig The role of antimicrobials in disrupting microbial
Flora

53. Summary of antimicrobial drugs, the primary tissues affected, and the damage produced.
Table 12.6 Major adverse toxic reactions to common drug groups.

54. Effective drugs Identify infectious agent Sensitivity testing
Minimum Inhibitory Concentration (MIC)

55. Sensitivity test such as the Kirby-Bauer Test can be used to determine the effectiveness of a drug by measuring the zone of inhibition.
Table 12.7 Results of a sample kirby-bauer test

56. An example of the Kirby-Bauer Test.
Fig Technique for preparation and interpretation
of disc diffusion test.

57. The E-test is an alternative to the Kirby-Bauer procedure.
Fig Alternative to the Kirby-Bauer

58. The dilution test is an effective method of determining the MIC.
Fig Tube dilution test for determining the MIC

59. The lower the MIC, the more effective the drug is toward combating the bacterium.
Table 12.8 Comparative MICs