Antimicrobial Chemotherapy 5 - tetracyclines

Question 1

What is the principle of the inhibition of protein synthesis in antibiotics?

Answer 1

Selective inhibition of bacterial protein synthesis by interference with functions of the 70S ribosome has yielded many clinically important antibiotics
- macrolides (MLS)
- tetracyclines
- AGACs
- chloramphenicol
- oxazolidinone

Ø The majority of existing inhibitors bind to the 16s or 23s rRNA components of the ribosome

Ø The diversity of inhibitor structures reflects the existence of multiple binding sites in rRNA arising from the variety of secondary and tertiary structural arrangements presented by these macromolecules

Question 2

Which part of the ribosome do most protein synthesis inhibitors bind to?

Answer 2

16S or 23S rRNA components

Question 3

Why is there such a diversity in inhibitor structures?

Answer 3

The diversity of inhibitor structures reflects the existence of multiple binding sites in rRNA arising from the variety of secondary and tertiary structural arrangements presented by these macromolecules

Question 4

Give examples of types of tetracyclines

Answer 4

Tetracycline
Doxycycline
Minocycline
Tigecycline

Question 5

What is the target of tetracyclines?

Answer 5

30s ribosome

Question 6

Give examples of macrolides

Answer 6

Erythromycin
Azithromycin
Clarithromycin

Question 7

What is the target of macrolides?

Answer 7

50s ribosome

Question 8

Give examples of aminoglycoside-aminocyclitol (AGAC) antibiotics

Answer 8

Amikacin
Streptomycin
Gentamicin
Tobramycin

Question 9

What are the advantages of aminoglycoside-aminocyclitol (AGAC) antibiotics?

Answer 9

Useful in penicillin allergic patients

Question 10

What is the target of aminoglycoside-aminocyclitol (AGAC) antibiotics?

Answer 10

30s ribosome

Question 11

Give an example of a lincosamide

Answer 11

Clindamycin

Question 12

What is the target of lincosamides?

Answer 12

50s ribosome

Question 13

What is the target of chloramphenicol?

Answer 13

50s ribosome

Question 14

What is the mechanism of tetracyclines?

Answer 14

Tetracycline binds to a single site in the 30s ribosomal subunit
- involves a region of 16s ribosomal RNA which contains base 892
- aminoacyl tRNA anti-codon is spatially proximal to the 16s RNA region containing base number 1400
- tetracyclines interfere with the folding of the 892-1400 region and hence aminoacyl tRNA from binding

Once inside the cell, tetracyclines bind reversibly to the 30S ribosomal subunit at a position that blocks the binding of the aminoacyl-tRNA to the acceptor site on the mRNA-ribosome complex

Question 15

What does MLS stand for?

Answer 15

Macrolides
Lincosamides
Steptogramins

Question 16

What is the mechanism of MLS antibiotics?

Answer 16

MLS selectively inhibit protein synthesis by binding the 50s subunit
MLS are bacteriostatic
- they do not kill bacteria
- prevents multiplication of bacteria
- reversible

Macrolides - binding of macrolides causes dissociation of peptidyl-tRNA from ribosomes
Macrolides block translocation
- causes release of an incomplete polypeptide from the ribosome
Streptogramins are bacteriostatic when used individually but bactericidal when Quinupristin/Dalfopristin are used together