INHIBITORS OF PROTEIN SYNTHESIS I Flashcards
How much does the ribosome make up of the dry weight of bacterial cells?
30%
How many proteins and RNA strands make up a ribosome?
Around 55 proteins and 3 strands of RNA
Why are ribosomes a good antibacterial target?
Protein synthesis must continue even when cells are dormant or slow-growing (e.g. in biofilm or a mycobacterium), so targeting the ribosome, will target all bacterial cells
How much energy can protein synthesis take up of a bacterial cell?
Up to 40%
What is tetracycline biosynthesized from?
From acetate, by species of Streptomyces
What components does tetracycline bind?
- Nucleic acid
- Proteins
- Ribosomes (only this bind inhibits cell function)
What’s the mechanism of action of tetracycline?
Tetracycline prevents amino-acyl tRNA from binding to the elongation factor TU on the 30S ribosomal subunits = prevents the protein chain from growing
How are bacteria resistant to tetracycline?
- Cell membrane modifications (changes to permeability to drug and use of efflux pumps)
- mutations in the S10 ribosomal protein also cause resistance (prevent binding)
Why are tetracyclines contraindicated in children?
They stain growing tooth enamel
What’s chlortetracycline used for?
Conjuctivitis in cats
What’s oxytetracycline used to treat and why is it used?
Acne and oxytetracycline is used because it’s well absorbed
What’s demeclocycline used for? (2)
Treats Lyme disease and SIADH (syndrome of inappropriate antidiuretic hormone)
What’s doxycycline used for? (2)
It is an antibacterial and used for malaria prophylaxis
What’s lymecycline used for and why is it used?
- Used to treat severe acne
- Lymecycline is 5000x more soluble than tetracycline + well-tolerated
What’s minocycline used for and why is it able to treat this disease?
- Treats Neisseria meningtidis.
- It’s a broader spectrum AB than other tetracyclines
What are some examples of aminoglycoside antibiotics? (4)
- Gentamycin
- Streptomycin
- Kanamycin
- Neomycin
What’s the chemical structure of aminoglycoside antibiotics?
Aminoglycoside contain several sugar rings and min. of one amino acids
What’s the mechanism of action of aminoglycosides?
- Binds to 30S ribosomal subunits, specifically 16S RNA
- Binding of Aminoacyl-tRNA to the A site is inhibited – no peptide bonds formed
- Genetic code is misread
What type of gram bacteria is aminoglycosides most effective against?
Very active against gram -ve bacteria
Disrupts the cell wall
Why are aminoglycoside antibiotics not used that often? (3)
- Has to be given by intramuscular injection because they are hydrophilic
- Has a very narrow therapeutic index - toxic
- Show nephotoxicity
Why is Gentamicin different from other aminoglycoside antibiotics?
Gentamicin is derived from Micromonospora, not Streptomyces (like other aminoglycosides)
- Gentamicin is also the most successful of the aminoglycosides
How does tobramycin work?
Binds to 30S and 50S ribosomal subunits, preventing them combining.
What is tobramycin used to treat and how is it used?
- For Pseudomonas aeruginosa infections
- Inhaled by cystic fibrosis patients
What is amikacin derived from and what’s it used to treat?
- Kanamycin
- Treats serious, hospital-acquired Gram negative infections
