1. Chapter 10 Controlling microbial growth in the body: Antimicrobials

2. Like disinfectants antimicrobial drugs act by killing or inhibiting the growth of microorganisms.
Antimicrobial drugs must act within the body and show _______________________.

3. Antimicrobial Drugs Chemotherapy: the use of drugs to treat a disease
Antimicrobial drugs: interfere with the growth of microbes within a host
Selective toxicity: killing harmful microbes without damaging the host

5. Representative Sources of Antibiotics
Insert Table 20.1

6. Spectrum of Activity
________________: Antibiotic affects a large number of Gram-positive or Gram-negative bacteria
________________: Affective against a small range of organisms
Penicillin G affects Gram-positive bacteria but very few Gram-negatives

7. The Spectrum of Activity of Antibiotics and Other Antimicrobial Drugs

8. Spectrum of Activity
Use of broad spectrum drugs also destroy ______ _______________
Survivors may become _______________
Yeast infections may arise from the over growth of Candida albicans
_______________
Term is also applied to growth of a target pathogen that has developed resistance to the antibiotic
Antibiotic resistant strain replaces the original sensitive strain and the infection continues

9. Antibiotics are only effective against ________ infections
________(flu) and ______________are _____ infections therefore antibiotics are ineffective!

10. Inhibition of Cell Wall Synthesis
Most common agents prevent cross-linkage of NAM subunits
Beta-lactams are most prominent in this group
Functional groups are beta-lactam rings
Beta-lactams bind to enzymes that cross-link NAM subunits
Bacteria have weakened cell walls and eventually lyse

11. Inhibition or degrading bacterial cell walls.
Tetrapeptide side chain
N-acetylglucosamine (NAG)
N-acetylmuramic acid (NAM)
Peptide cross-bridge
Side-chain amino acid
Cross-bridge amino acid
NAM
Peptide
bond
Carbohydrate
“backbone”
NAG
Structure of peptidoglycan in
gram-positive bacteria .

12. Inhibition or degrading bacterial cell walls.
Penicillin's
Cephalosporin's
Vancomycin

13. The inhibition of bacterial cell synthesis by penicillin.
Rod-shaped bacterium before penicillin.
The bacterial cell lysing as penicillin weakens the cell wall.

14. One of the most successful groups of antibiotics targets the synthesis of bacterial cell walls; why does the antibiotic not affect the mammalian cell?

15. Protein synthesis site 70S prokaryotic ribosome
The inhibition of protein synthesis by antibiotics.
Protein synthesis site
Growing polypeptide
Tunnel
Growing polypeptide
50S 5′
Chloramphenicol
Binds to 50S portion and inhibits formation of peptide bond
30S
50S portion 3′
mRNA
Three-dimensional detail of the protein synthesis site showing the 30S and 50S subunit portions of the 70S prokaryotic ribosome
Protein synthesis site
tRNA
Messenger RNA
30S portion
Direction of ribosome movement
Streptomycin
Tetracyclines
70S prokaryotic ribosome
Changes shape of 30S portion,
causing code on mRNA to be
read incorrectly
Interfere with attachment of
tRNA to mRNA–ribosome complex
Translation
Diagram indicating the different points at which chloramphenicol, the tetracyclines, and streptomycin exert their activities

16. Inhibitors of Protein Synthesis
Prokaryotic ribosomes are 70S (30S and 50S)
Eukaryotic ribosomes are 80S (40S and 60S)
Drugs can selectively target translation
Mitochondria of animals and humans contain 70S ribosomes
Can be harmful

17. Inhibitors of Protein Synthesis
Chloramphenicol
Broad spectrum
Binds 50S subunit; inhibits peptide bond formation

18. Inhibitors of Protein Synthesis
Aminoglycosides
Streptomycin
Broad spectrum
Change shape of 30S subunit
Can have fatally toxic effects on Kidneys

19. Inhibitors of Protein Synthesis
Tetracyclines
Broad spectrum
Interfere with tRNA attachment
Side effects? Should Children take tetracycline?
Children may experience a brown discoloration of teeth
Pregnant women may cause liver damage
Most common antibiotic added to animal feed
Use results in significantly faster weight gain

20. Inhibition of nucleic acid replication and transcription

21. Inhibitors of Nucleic Acid Synthesis
Several drugs block DNA replication or mRNA transcription
Drugs often affect both eukaryotic and prokaryotic cells
Not normally used to treat infections
Used in research and perhaps to slow cancer cell replication

22. Inhibitors of Nucleic Acid Synthesis
Rifamycin
Inhibits RNA synthesis
Antituberculosis

23. Injury to the plasma membrane of a yeast cell caused by an antifungal drug.

24. Injury to the Plasma Membrane
Some drugs form channel through cytoplasmic membrane and damage its integrity
Polymyxin B
Topical
Combined with bacitracin and neomycin in over-the-counter preparation

25. Inhibiting the Synthesis of Essential Metabolites: Antimetabolics
Antimetabolic agents can be effective when metabolic processes of pathogen and host differ
Sulfonamides (sulfa drugs)
Inhibit folic acid synthesis
Broad spectrum

26. Inhibiting the Synthesis of Essential Metabolites: Antimetabolics

27. Action of Enzyme Inhibitors
Figure 5.7bc Enzyme inhibitors.
Action of Enzyme Inhibitors
Competitive
inhibitor
Altered
active site
Noncompetitive
inhibitor
Allosteric
site

28. Major Action Modes of Antimicrobial Drugs.
1. Inhibition of cell wall synthesis: penicillins, cephalosporins, bacitracin, vancomycin
2. Inhibition of protein synthesis: chloramphenicol, erythryomycin, tetracyclines, streptomycin
DNA
mRNA
Protein
Transcription
Translation
Replication
Enzyme
4. Injury to plasma membrane: polymyxin B
5. Inhibition of essential metabolite synthesis: sulfanimide, trimethoprim
3. Inhibition of nucleic acid replication and transcription: quinolones, rifampin

29. Clinical Considerations in Prescribing Antimicrobial Drugs
Routes of Administration
Topical application of drug for external infections
Oral route requires no needles and is self-administered
Intramuscular administration delivers drug via needle into muscle
Intravenous administration delivers drug directly to bloodstream 29

30. Administration method
Figure The effect of route of administration on blood levels of a chemotherapeutic agent
Administration method
Oral
Intramuscular (IM)
Relative concentration of drug in blood
Continuous intravenous (IV)
Time (hours)

31. Clinical Considerations in Prescribing Antimicrobial Drugs
Safety and Side Effects
Toxicity
Cause of many adverse reactions poorly understood
Drugs may be toxic to kidneys, liver, or nerves
Consideration needed when prescribing drugs to pregnant women
Allergies
Allergic reactions are rare but may be life threatening
Anaphylactic shock 31

32. Black hairy tongue caused by antiprotozoan drug metronidazole (Flagyl)
Figure Some side effects resulting from toxicity of antimicrobial agents-overview
Black hairy tongue caused by antiprotozoan drug metronidazole (Flagyl)
Temporary and Harmless!
Discoloration and damage to tooth enamel caused by tetracycline

33. Resistance to Antimicrobial Drugs
The Development of Resistance in Populations
Some pathogens are naturally resistant
Resistance by bacteria acquired in two ways
New mutations of chromosomal genes
Acquisition of R-plasmids via transformation, transduction, and conjugation

34. Antibiotic Resistance
Misuse of antibiotics selects for resistance mutants
Misuse includes:

35. Clinical Focus Antibiotics in Animal Feed Linked to Human Disease, Figure A.
Cephalosporin-resistance in E. coli transferred by conjugation to Salmonella enterica in the intestinal tracts of turkeys.
after conjugation
S. enterica
S. enterica
E. coli
Resistance plasmid

36. Antibiotic Resistance
At least 6 mechanisms of microbial resistance

37. Effects of Combinations of Drugs
__________occurs when the effect of two drugs together is greater than the effect of either alone
___________occurs when the effect of two drugs together is less than the effect of either alone

38. Area of synergistic inhibition, clear Area of growth, cloudy
Figure An example of synergism between two different antibiotics.
Area of synergistic inhibition, clear
Area of growth, cloudy
Disk with antibiotic amoxicillin-clavulanic acid
Disk with antibiotic aztreonam