lecture 5 - antibiotic control of bacterial infections

Question 1

Why do antibiotics have a differential toxicity for bacterial cells vs human/eukaryotic cells?

Answer 1

The bacterial cells have targets not present in eukaryotic cells OR target is sufficiently different in eukaryotic cells

Question 2

What are the 3 categories of antibiotic, based on cellular target?

Answer 2

Cell wall synthesis, nucleic acid synthesis, protein synthesis

Question 3

What is the difference between the gram-positive and gram-negative cell wall?

Answer 3

gram-positive: thick peptidoglycan layer
gram-negative: thin peptidoglycan layer with outer lps membrane

Question 4

What protein is a target for penicillin binding, and is responsible for peptide side chain cross-linking in the peptidoglycan layer of the bacterial cell wall?

Answer 4

penicillin-binding protein

Question 5

What are Beta-lactams?

Answer 5

A class of antibiotic that all contain a beta-lactam ring in their chemical structure

Question 6

What are the 4 classes of Beta-lactam antibiotics?

Answer 6

Penicillin, cephalsporin, carbapenem, monobactam

Question 7

What chemically differentiates the classes of Beta-lactam antibiotics?

Answer 7

The R side chains of the Beta-lactam rings

Question 8

What protein is produced by bacteria and makes them resistant to some classes of Beta-lactam antibiotics?

Answer 8

Beta-lactamases - they break down beta-lactams

Question 9

What class of beta-lactam is most likely to cause an allergic reaction?

Answer 9

Penicillin

Question 10

What is the function of penicillin-binding protein?

Answer 10

Crosslinking of the peptide side chains of peptidoglycan backbone in the bacterial cell wall

Question 11

What are the 2 key classes of glycopeptides (antibiotics)?

Answer 11

vancomycin, teicoplanin

Question 12

What class of bacteria are affected by glycopeptide antibiotics, e.g. vancomycin ?

Answer 12

gram-positive only

Question 13

Why are glycopeptide antibiotics unable to target gram-negative bacteria?

Answer 13

They are unable to penetrate the gram-negative outer membrane

Question 14

How do glycopeptides kill bacteria?

Answer 14

They bind to components of the bacterial peptidoglycan layer to inhibit cross linking

Question 15

How do protein synthesis inhibitor antibiotics work?

Answer 15

By binding to RNA in the ribosome functional sites to prevent bacterial protein synthesis

Question 16

Why do protein synthesis inhibitors have differential specificity between host cells and bacterial cells?

Answer 16

The prokaryotic and eukaryotic ribosomes are structurally different so the human ribosome is not a target

Question 17

Which class of antibiotics include antibiotics that target folate synthesis?

Answer 17

Nucleic acid synthesis antibiotics

Question 18

How do folate synthesis targeting antibiotics work?

Answer 18

They competitively inhibit enzymes in the folate synthesis pathway preventing the production of tetrahydrofolic acid, which is essential for nucleic acid synthesis

Question 19

How do fluoroquinolone antibiotics work?

Answer 19

They inhibit bacterial type II topoisomerase enzymes which inhibits DNA replication

Question 20

What is the function of type II topoisomerase enzymes in bacteria?

Answer 20

They introduce negative supercoils that are required for bacterial DNA packaging

Question 21

How does Rifampicin antibiotic work?

Answer 21

Inhibits RNA synthesis by targeting DNA polymerase

Question 22

How does the antibiotic metronidazole work?

Answer 22

Makes breaks in bacterial DNA preventing nucleic acid synthesis, but leaves human DNA intact

Question 23

What are prodrugs?

Answer 23

Drugs that become active once they have entered the body