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Antimicrobial Drugs. How were antimicrobial drugs first discovered?. Alexander Fleming 1928 S. aureus, Penicillium notatum Mass production: 1940s Antibiosis Lead to antibiotic Different from chemotherapy!. Where do antibiotics come from?. From other bacteria found in Soil Bacteria

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how were antimicrobial drugs first discovered
How were antimicrobial drugs first discovered?
  • Alexander Fleming
    • 1928
    • S. aureus,
    • Penicillium notatum
    • Mass production: 1940s
  • Antibiosis
    • Lead to antibiotic
    • Different from chemotherapy!
where do antibiotics come from
Where do antibiotics come from?
  • From other bacteria found in
    • Soil
      • Bacteria
        • Streptomyces: more than half!
        • Bacillus
      • Molds
        • Penicillium
        • Cephalosporium
what is an antibiotic s spectrum
What is an antibiotic’s 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
how do antimicrobial drugs work
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
how can an antibiotic destroy the cell wall
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
can you discuss some examples
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
how can they inhibit protein synthesis
How can they inhibit protein synthesis?
  • Tetracyclines, chloramphenicol, streptomycin, etc.
how do they injure the pm
How do they injure the PM?
  • Polypeptide antibiotics (e.g. polymyxin B)
  • Change permeability of PM
how do they inhibit dna synthesis
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
how do they inhibit synthesis of important metabolites
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 don’t make folic acid, we eat it!
      • Broad spectrum
what are some antifungal drugs
What are some antifungal drugs?
  • Many target fungal sterols
    • Ergosterol vs. (humans) cholesterol
    • Azoles
      • Athlete’s foot, yeast infection treatment
  • Others target chitin cell wall
    • Echinocandins
  • Many others which we won’t worry about…
what about antiviral drugs
What about antiviral drugs?
  • Very few… WHY????
  • Drugs can attack
    • Attachment
    • Penetration
    • Uncoating
    • DNA/RNA synthesis
    • Virion assembly
can you tell me about a couple
Can you tell me about a couple?
  • Nucleosides and nucleotide analogs
    • Acyclovir: genital herpes
    • Interferons
what tests are used to identify antimicrobial activity
What tests are used to identify antimicrobial activity?
  • Disk-diffusion
    • Can’t determine bactericidal vs. stasis
  • Gradient diffusion
  • Broth dilution
    • Can determine bactericidal vs. -stasis
effects of combinations of drugs
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
is there a downside to antimicrobial or antibiotic use
Is there a downside to antimicrobial or antibiotic use?
  • Yes!
  • Natural selection
  • Antibiotics
    • Always take the full prescription
    • They don’t work on viruses!
what types of resistance are there
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
future of chemotherapeutic agents
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