Antibiotics affecting Protein Synthesis

Question 1

Difference between Eukaryotic and Prokaryotic Ribosomes

Answer 1

Eukaryotic: 80S made from 60S & 40S
Prokaryotic: 70S made from 50S & 30S

Question 2

Steps in Protein Synthesis

Answer 2

1. Amino Acid activation: putting AA on tRNA
2. Form Initiation complexes: 30S complex w/ tRNA and mRNA; 50S subunit comes in 2nd
3. Polypeptide chain synthesis
   a. Recognition: codon-anti-codon
   b. Peptidyl transfer: peptide bond
   c. Translocation and release

Question 3

Amino Acid Activation Inhibitors

Answer 3

• No clinically significan inhibitors of amino acid activation
• B/c charging mechanism similar b/t humans and bacteria

Question 4

Linezolid

Answer 4

-Initiation Complex Inhibitors
-Linezolid: inhibits formation of 70S initiation complex
-Binds 50S blocking ternary complex formation
-Bacteriostatic for staphlococci and eterococci
-Bactericidal for streptococci
+differnt b/c stronger action as competitive inhibitor

Question 5

Peptide Chain Synthesis: Recognition inhibition: Aminoglycosides

Answer 5

• Ex. Streptomycin
• Broad spectrum
• bactericidal
• Selective toxicity: Targets proteins in 30S subunit and uptake by bacteria only
• MOA:
  
  1. Misreading- insert wrong amino acid due to codon distortion
  2. Cyclic polysomal blockade: 70S forms but falls apart
  3. Faulty outer membrane proteins
• effective against pseudomonas, ineffective w/ intracellular bacteria
• Resistance:
  
  1. Altered 30S target
  2. Decreased uptake by cell
  3. Enzyme alteration of aminoglycoside

Question 6

Peptide Chain Synthesis: Recognition inhibition: Spectinomycin

Answer 6

• Bacteriostatic
• Forms ustable 70S initiation complexes
• Tx for beta-lactamase gonorrhea

Question 7

Tetracyclines

Answer 7

• Inhibit recognition
• Broad spectrum
• Bacteriostatic
• Tx: chlamydia mycoplasma rickettsia (intracellular pathogens)
• Selective toxicity: bacteria high affinity uptake and target 70S
• Bind 30S and inhibit binding of aa-tRNA to A site
• Resistance: Decreased uptake
  
  • Efflux
  • Elongation factor proteins that protect 30S

Question 8

Chloramphenicol

Answer 8

• Inhibitors of peptidyl transfer
• Broad specturm
• Bacteriostatic
• Binds reversibly to 50S and alters tRNA structure blocking peptidyl transfer
• Selective toxicity: can’t enter mitochondria
  
  • Doesn’t bind host 60S
• Resistance: plasmid associated acetyltransferase acetylates -OH groups preventing 50S binding

Question 9

Lincomycin & Clindamycin

Answer 9

• Inhibits peptidyl transfer
• Narrow spectrum: G+ (Staph) or anaerobic G-
• Bacteriostatic
• Similar MOA as chloramphenicol (binds 50S)
• Resistance: metylation 23S rRNA prevents drug binding to 50S

Question 10

Macrolides

Answer 10

• Inhibits translocation
• Medium Spectrum
• Bacteriostatic
• Tx: Mycoplasma, Legionella, Chlamydia, Campylobacter
• Azithromycin, Clarithromycin, Erythromycin
• MOA unknown
• Resistance: 23S methylation preventing binding
  
  • Lactone ring hydrolysis by esterase
  • Drug efflux

Question 11

Streptogramins

Answer 11

-Translocation inhibitors

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