Antimicrobials: Part 4: MOAs of drugs that affect protein synthesis

Question 1

What is the MOA of aminoglycosides?

Answer 1

Irreversible inhibition of the translation initiation complex by binding to the 30S subunit → misreading of mRNA and blocks translocation

Question 2

What is the one very unique feature of aminoglycosides MOA?

Answer 2

This drug is bactericidal!!
This is a unique feature.
The misread proteins go to cell surface→ cell becomes more permeable → cell death

Question 3

What do aminoglycosides require for uptake?

Answer 3

Requires O2 for uptake, so it won’t work for anaerobes!

Question 4

How does resistance to aminoglycosides work?

Answer 4

Bacteria acquire enzymes that will modify the antibiotic structure via phosphorylation, adenylation, acetylation

Question 5

What is the MOA of tetracycline?

What is the resistance mechanism?

Answer 5

Binds to the 30S subunit and prevents the attachment of aminoacyl-tRNA

Resistance: bacterial develop ways to increase influx or really decrease eflux

Question 6

What is the MOA of tigecycline?

Answer 6

Binds to the 30S subunit → inhibits protein synthesis

Question 7

What is the MOA of macrolides?

What is the resistance mechanism?

Answer 7

Blocks translocation by binding the the 23S rRNA of the 50S ribosomal subunit

Important resistance mechanism: 23S rRNA of the 50S ribosomal subunit becomes methylated!

Question 8

What is the MOA of chloramphenicol?

Answer 8

Binds to 50S at the A site and blocks peptidyltransferase

Question 9

What is the MOA of clindamycin?

What is the resistance mechanism?

Answer 9

MOA: Same as macrolides
Resistance: same as macrolides!!

Question 10

What is the MOA of linezolid?

Answer 10

Inhibition of the translation initiation complex by binding to the 50S subunit

Just like aminoglycosides!

Question 11

What is the MOA of streptogranins?

Answer 11

Inhibition of the translation by binding to the 50S subunit

Antibiotics of last resort