Antibiotics

• How do we kill microbes once they infect us?

  • immune system
  • Chemotherapy
• what differences do we exploit from microbes?

  • different structure
  • different metabolism
• What is a chemotherapeutic agent?

  Any chemical used to improve the body’s health
• What are antibiotics used for?

  Bacteria, fungi, Protozoa
• what are antivirals used for?

  virus
• Antimicrobial chemotherapuetics must be _

  Selective
• Selective toxicity means…


  It targets the microbe
• Antibiotics are usually of _ origin

  Natural
• Some antibiotics have been __ but most come from __

  Synthesized, microbes
• antibiotics inhibit other microbes in __ amounts

  Small
• What is “spectrum of activity”

  is the range of microbes the antibiotic is effective against
• Erythromycin has a _ spectrum

  Narrow —> works against gram+ve
• Tetracyline is an antibiotic with a _ spectrum


  Broad
• What are some Methods of antimicrobial activity?

  Inhibits protein synthesis

  Inhibits cell wall synthesis

  Injures plasma membrane

  Inhibits nucleic acid synthesis

  Inhibits essential metabolite synthesis
• Where do antibiotics originally come from?

  Microbial wars

  1. Streptomyces bacteria (Main source)
  2. Synthetic
  3. Gram+ve bacilli
  4. Penicillin Fungus
• What are the types of non-microbial antibiotics?

  1. Sulfonamides
  2. Isoniazid
  3. Quinolones
  4. Quinine
• Sulfonamides? 


  Eg. Sulfanilamide

  1st significant chemotherapeutic agent

  Synthetic and isolated from red clothing dye in 1935

  inhibits folic acid synthesis

  Mimics folic acid precursors.
• Does bacteria need folic acid to synthesize nucleic acid?

  Yes
• What type of spectrum are Sulfonamides?

  Broad (both + and -)

  Sulfamethoxazole —> treats UTI

  Sulfisoxazole —> treats vaginal infection
• Isoniazid?

  • stops my colic acid synthesis
  • Synthesized in 1912
  • Activated to toxic form by catalase in bacteria
  • Inhibits mycolic acid production
  • Used against TB and Leprosy
• Quinolones?

  • ends in oxacin
  • Synthesized in early 1960’s
  • Inhibits DNA synthesis
  • Treats UTI’s with Sulfonamides resistant bacteria
• Quinine?

  • Derived from cinchona tree bark
  • Antimalaria
  • binds to Protozoa DNA (plasmodium) and inhibits reproduction.
• What are the microbial derived antibiotics?

  Parents….

  • Penicillin
  • cephalosporin
  • Streptomycin
  • Chloramphenicol
  • Tetracycline
  • Polymyxins
• Penicillin?

  • discovered by accident in 1928 by Alexander Fleming
  • Derived from penicillin mold
  • Beta-lactame ring
  • Inhibits peptidoglycan synthesis by squeezing between protein and carb
• What are the advantages of penicillin derivatives?

  • increased bioavailability
  • Stomach acid resistance
  • Less sticking to food
  • Increased absorption
  • Greater half lives
• What are the disadvantages of penicillin derivatives?

  • less effective (decreased spectrum)
  • Organ damage (stomach, kidney, liver)
  • anaphylactic reactions
  • Antibiotic resistance
• Streptomycin?

  • from streptomyces bacteria
  • From aminoglycoside family
  • Binds and inhibits ribosomes
  • Toxic/ not well absorbed
  • Effective against intestinal infection and as a topical ointment.
• Chloramphenicol?

  • from streptomyces bacteria
  • Stops protein synthesis
  • Broad spectrum
  • Very tissue invasive
  • Affective against meningitis
• What are the side effects of chloramphenicol?

  Aplastic anemia

  Gray syndrome in newborns
• Tetracycline?

  • from streptomyces bacteria
  • Stops protein synthesis
  • Broad spectrum
  • treats STD’s
• What are the side effects of tetracycline?

  • stunted bone growth in kids
  • Teeth discolouration
• Polymyxins?

  • from bacillus Polymyxa (gram+ve)
  • Lipopeptide antibiotic
  • Disrupts outer membrane of gram-ve bacteria
  • Neurotoxic
  • Last resort antibiotic for superbugs
  • Only works for gram-ve
• What are the two ways to test the effectiveness of an antibiotic?

  1. Diffusion Methods
  2. Broth-dilution test
• What are the two types of diffusion methods?

  Below

  A) Kirby Bauer Test

  B) E-test

  
• What is a Kirby Bauer Test?

  • filter paper soaked in antibiotic
  • Paper placed in plate with growing bacteria
  • Zone of Inhibition indicates effectiveness.
  • (unable to see if it is bacteriocidal, it is qualitative)

  
• What is an E-test?

  • plastic strip coated with gradient of antibiotic
  • Strip is placed on plate with growing bacteria
  • Tells you MIC of antibiotic (minimum inhibitory concentration)

  
• What is a broth dilution test?

  • Antibiotic is diluted into wells, containing bacteria broth
  • Let bacteria grow
  • Lowest concentration of antibiotic that shows no growth of bacteria = MIC
  • Can check if bacteriocidal.

  
• What are some antifungal chemotherapeutics?

  1. Nystatin
  2. Amphoteracin B
  3. Imidazoles
  4. Triazoles
• Nystatin?

  • From streptomyces bacteria
  • Binds to sterols in membrane of fungus, changing permeability.
  • Treats Candida albicans yeast infection
  • Combines with broad spectrum antibiotics to prevent candida overgrowth
• Amphotericin B

  • From streptomyces
  • Used for serious fungal infection
  • Binds sterols and degrades membranes
  • Lots of side effects