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Antimicrobial Drugs

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... transposons Resistance to Antibiotics Antimicrobial peptides Broad-spectrum antibiotics Nisin (lactic acid bacteria) Magainin (frogs) Cecropin (moths) ... – PowerPoint PPT presentation

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Title: Antimicrobial Drugs


1
Antimicrobial Drugs
2
How were antimicrobial drugs first discovered?
  • Alexander Fleming
  • 1928
  • S. aureus,
  • Penicillium notatum
  • Mass production 1940s
  • Antibiosis
  • Lead to antibiotic
  • Different from chemotherapy!

3
Where do antibiotics come from?
  • From other bacteria found in
  • Soil
  • Bacteria
  • Streptomyces more than half!
  • Bacillus
  • Molds
  • Penicillium
  • Cephalosporium

4
What is an antibiotics spectrum?
  • Number/types of organisms it affects
  • Narrow spectrum of antibiotic activity
  • Penicillin G mostly only gram
  • Broad spectrum antibiotic activity
  • Tetracycline
  • Pros vs cons
  • Lead to
    superinfections

5
How do antimicrobial drugs work?
  • Depends on the drug
  • Bactericidal or bacteristatic
  • Modes of action include
  • Cell wall destruction
  • Inhibiting transcription or translation
  • Plasma membrane damage
  • Inhibiting DNA synthesis
  • Inhibiting synthesis of metabolites

6
How can an antibiotic destroy the cell wall?
  • Penicillin and others
  • Prevent synthesis (crosslinking)
  • Cell then lyses due to weakened wall
  • Only affects actively growing cells
  • Does not affect humans

7
Can you discuss some examples?
  • Penicillin
  • Penicillin G
  • Narrow spectrum, penicillinase susceptible
  • Penicillinase-resistant penicillins
  • Methicillin
  • MRSA
  • Replacing methicillin oxacillin, nafcillin
  • Extended spectrum penicillins
  • Ampicillin, amoxicillin
  • Effective against both gram and
  • Cephalosporins
  • Penicillinase resistant, gram effective
  • Vancomycin
  • Narrow spectrum
  • Last resort

8
How can they inhibit protein synthesis?
  • Tetracyclines, chloramphenicol, streptomycin,
    etc.

9
How do they injure the PM?
  • Polypeptide antibiotics (e.g. polymyxin B)
  • Change permeability of PM

10
How do they inhibit DNA synthesis?
  • Limited usefulness WHY?
  • Quinolones
  • Inhibits DNA gyrase
  • UTIs
  • Fluoroquinolones
  • Ciprofloxacin (Cipro)
  • Affects cartilage development
  • Can be used in adults

11
How do they inhibit synthesis of important
metabolites?
  • Competitive inhibition
  • Synthetic drug
  • Sulfaniamide inhibits para-aminobenzoic acid
    (PABA)
  • PABA is precursor for making folic acid
  • Sulfa prevents conversion
  • Humans dont make folic acid, we eat it!
  • Broad spectrum

12
What are some antifungal drugs?
  • Many target fungal sterols
  • Ergosterol vs. (humans) cholesterol
  • Azoles
  • Athletes foot, yeast infection treatment
  • Others target chitin cell wall
  • Echinocandins
  • Many others which we wont worry about

13
What about antiviral drugs?
  • Very few WHY????
  • Drugs can attack
  • Attachment
  • Penetration
  • Uncoating
  • DNA/RNA synthesis
  • Virion assembly

14
Can you tell me about a couple?
  • Nucleosides and nucleotide analogs
  • Acyclovir genital herpes
  • Interferons

15
What tests are used to identify antimicrobial
activity?
  • Disk-diffusion
  • Cant determine bactericidal vs. stasis
  • Gradient diffusion
  • Broth dilution
  • Can determine bactericidal vs. -stasis

16
Effects of Combinations of Drugs
  • Synergism occurs when the effect of two drugs
    together is greater than the effect of either
    alone
  • Antagonism occurs when the effect of two drugs
    together is less than the effect of either alone

17
Whats next?
18
Is there a downside to antimicrobial or
antibiotic use?
  • Yes!
  • Natural selection
  • Antibiotics
  • Always take the full prescription
  • They dont work on viruses!

19
What types of resistance are there?
  • video
  • Destruction of the drug (e.g. penicillinase)
  • Prevention of drug penetration
  • Common with tetracycline
  • Alteration of drug target site
  • Rapid efflux
  • Heredity
  • Transformation, transduction, transposons

20
Resistance to Antibiotics
21
Future of Chemotherapeutic Agents
  • Antimicrobial peptides
  • Broad-spectrum antibiotics
  • Nisin (lactic acid bacteria)
  • Magainin (frogs)
  • Cecropin (moths)
  • Antisense agents
  • Complementary DNA that binds
  • a pathogen's virulence gene(s)
  • and prevents transcription
  • Fomivirsen to treat CMV retinitis
  • siRNA
  • Complementary RNA that binds mRNA to inhibit
    translation
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