Microbiology-Antibiotics against protein synthesis Flashcards
Eukaryotes have ribosomes just as prokaryotes do. Why then do antibiotics specifically target ribosomes.
Prokaryotic ribosomes (70S = 50S + 30S) and eukaryotic ribosomes (80S = 60S + 40S) have different size subunits. The real concern is that prokaryotic ribosomes and mitochondrial ribosomes are very similar. Luckily, it is very difficult for these antibiotics to cross the mitochondrial membrane.
What makes up the subunits of the 70S prokaryotic ribosomes?
30S = 16S rRNA + 21 different proteins 50S = 5S rRNA and 23S rRNA with lots of other proteins
How do you get to the 30S initiation complex in prokaryotic translation?
IF3 causes the 70S subunit to dissociate. IF1 and IF2 then bind to the 30S sub unit with GTP. mRNA and the charged fMet tRNA come in and form the initiation complex.
How do you get to the final 70S initiation complex before translation?
The initiation factors leave, 50S comes in and you’re good to go
How does peptide chain synthesis occur in translation?
Recognition of the correct tRNA anticodon at the A site, peptidyl transfer of the amino acid to the chain, translocation of tRNA and release of used tRNA.
What step of protein synthesis does not have a clinically significant inhibitor? Why?
Amino acid activation. This is because charging of tRNA molecules is a universal process between eukaryotes and prokaryotes.
You prescribe a drug to a patient that inhibits protein synthesis before it is ever charged with a tRNA. This drug should never be used for catheter or gram - infections. What is the drug and how does it work?
Linezolid (Zyvox) which is from the class of oxazolidinone antibiotics. They prevent formation of the 70S initiation complex. How strongly the drug binds to the subunit determines whether it is bacteriostatic or bactericidal.
What drugs target the recognition step of translation? How do they work?
Aminoglycosides. They can target specific proteins in the A site codon of the 30S subunit. This causes misreading by the ribosome. The can cause the 70S initiation complex to be unstable and blocks formation of polysomes. They can also cause defects in the outer membrane proteins.
If a bacteria is resistant to streptomycin will it be resistant to neomycin?
No. Aminoglycosides have the same mechanism of action and act on different ribosomal proteins.
Why are aminoglycosides a concern for patients on dialysis?
They induce biofilm formation by bacteria
How do bacteria become resistant to amino glycosides?
Alter 30S subunit, decrease uptake of drug and enzymatic modifications to the amino glycoside (acetylation of the antibiotic).
A patient comes to see you with gonorrhea. What is normally prescribed and how does it work?
Spectinomycin. It is a bacteriostatic drug that causes formation of unstable 70S initiation complexes.
A patient comes to see you with chlamydia. What is normally prescribed and how does it work?
Tetracyclines. They can get into cells and attack intracellular bacteria. They broadly inhibit binding of incoming tRNA to A site on the 30S ribosome.
How do bacteria become resistant to tetracyclins?
Decrease uptake (OmpF porin mutation), efflux of drug from cell and elongation factor-like proteins that protect the 30S subunit.
This drug is not used in the US, but is used in many developing countries.
Chloramphenicol. It inhibits peptide bond formation by targeting the 50S subunit by altering tRNA structure and blocking peptidyl transfer.