LecTop8: Antibiotics

Question 1

Give definitions for bactericidal and bacteriostatic antibiotics.

Answer 1

Bactericidal: Kills microorganism
Bacteriostatic: Stops growth of bacteria.
Note: may be antagonistic. As seen with cell wall biosynthesis inhibitor, bactericidal antibiotics. They require a growing bacteria to kill. If patient also taking bacteriostatic antibiotic, makes bactericidal cell wall growth inhibitor ineffective.

Question 2

What is meant by Minimal Inhibitory Concentration (MIC)? How is MIC determined?

Answer 2

MIC is the goal to provide the smallest amount of antibiotic possible to a patient that is still affective. Determined as endpoint between growth and no growth of bacteria.

Question 3

What is selective toxicity? Example?

Answer 3

Selective toxicity = how selective an antibiotic is for a specific bacterial trait that is not shared with the host. Ex. Antibiotics that attack bacterial cell walls have NO affect on eukaryotes b/c we don’t have cell walls.

Question 4

What are the four antibiotics discussed in class that act by inhibition of cell wall (peptidoglycan) biosynthesis in bacteria? What are 3 broad traits of these antibiotics?

Answer 4

D-Cycloserine, Vancomycin, Basitracin, Penicillin.

1. All are bactericides
2. Only work against GROWING cell
3. Most potent class of antibiotics - due to selective toxicity.

Question 5

What is the mechanism by which D-cycloserine works?

Answer 5

D-cycloserine is a structural analog for D-alanine.

• D-cyclosine binds to D-alanine, which disrupts the D-alanyl-D-alanine compound that is added to the peptidoglycan precursor subunits.
• Cytoplasm stage of peptidoglycan formation.

Question 6

what is the mechanism by which Vancomycin works?

Answer 6

Vancomysin is a very large molecule that binds to peptidoglycan subunit precursor blocking their ability to cross the cytoplasmic membrane of the bacterial cell.

Question 7

What is the mechanism of Basitracin?

Answer 7

Basitracin is located outside of the cytoplasmic membrane and binds the 55C lipid shuttle, which ferries the peptidoglycan subunit precursor across the cytoplasmic membrane, and doesn’t allow it to release its second phosphate.
-The charged, basitracin bound, lipid shuttle can no longer get across the cytoplasmic membrane. This is a problem because this shuttle is too large to be continuously remade, therefore must be recycled.

Question 8

What is the mechanism of penicillin?

Answer 8

Penicillin is a structural analog to D-alanyl-D-alanine.

• Transpeptidase (Penicillin binding protein - PBP) is an enzyme that binds to D-alanyl-D-alanine and the peptidoglycan subunit precusors to form aa cross bridges.
• When Penicillin present, transpeptidase binds penicillin instead of D-alanyl-D-alanine. Thus, weak peptidoglycan with no cross links formed…doesn’t work.

Question 9

What structure do all penicillins contain that is essential to its antibiotic function?
-What type of bacteria is penicillin most effective against?

Answer 9

The B-lactam ring.
-Penicillin are most affective against Gram+ bacteria because they rely on the formation of an aa cross-link at every peptide side chain.

Question 10

What are the two families of antibiotics that disrupt cellular membranes? Describe mechanism of each.
-What is each most affective against?

Answer 10

1. Polymyxins: Alter permeability of membranes by binding to simple phospholipids.
   - These large antibiotic molecules insert into the membrane(s) and push adjacent phospholipids aways increasing permeability.
   - Most affective against Gram- bacteria because affect both membranes!
2. Polyenes: Alter permeability by binding to sterols in membrane.
   - Most affective against eukaryotes because prokaryotes do not have sterols in their membranes.

Question 11

What are the four antibiotics that act by inhibiting nucleic acid biosynthesis/DNA replication?

Answer 11

1. Quinilone
2. Metronidazole
3. Rifamycines
4. Sulfonamides

Question 12

What is the mechanism by which Quinilone works?

Answer 12

Quinilone inhibits DNA replication by disrupting the action of DNA Gyrase, which unwinds DNA to allow for transcription to initiate.

Question 13

What is the mechanism by which Metronidazole works?

-What type of bacteria is metronidazole most affective against?

Answer 13

Metronidazole disrupts DNA replication releasing oxygen free radicals.

• These oxygen free radicals damage DNA causing stoppage of DNA replication or replication of terminal genetic mutations.
• Most affective against anaerobic bacteria b/c they do not express the genes for the oxygen dismutase enzyme.

Question 14

What are the mechanisms of

• Rifamycin?
• Sulfonamide?

Answer 14

• Rifamycin inhibits DNA replication by binding to RNA polymerase (subunit B)
• Sulfonamides inhibit Nucleic Acid Synthesis by acting on enzymes involved in the process of producing nucleic acids.

Question 15

What do role do the three following antibiotics play?
-Kanamycin
-Tetracyclin
-Streptomycin
What is a possible side affect of kanamycin, tetracyclin, and streptomycin?

Answer 15

Kanamycin, tetracyclin, and streptomycin all act to inhibit translation of bacterial proteins by inhibiting the action of the 30s ribosomal subunit (Initiation complex).
-Possible side affect in humans is an attack on the 30s ribosome in mitochondria.

Question 16

What role do the following five antibiotics play?

• Chloramphenicol
• Erythromycin
• Azithromycin
• Clindamycin
• Lincomycin

Answer 16

Chloramphenicol, erythromycin, Azithromycin, clindamycin, and lincomycin all act to stop protein translation by binding to and inhibiting the 50s subunit in prokaryotic cells.

Question 17

These three antibiotics are often giving in conjunction to fight what type of bacterial infection? What is it about their physical structure that allows them to be affective?

1. Isoniazid (INH)
2. Pyrazinamide (PZA)
3. Ethambutal (EMB)

Answer 17

Isoniazid, Pyrazinamide, and ethambutal are all small, charged particles that inhibit mycolic acid biosynthesis by Mycobacterium tuberculosis.
-Used in treatment of tuberculosis

Question 18

What is the purpose of Bedaquilone?

Mechanism?

Answer 18

Bedaquilone is an antibiotic used to kill Mycobacterium stroptococcus.
-Bedaquilone works by inhibition of the Proton Pump used during ATP synthesis.

Question 19

What method is used to compare the relative effectiveness of antibiotics?

Answer 19

MIC = Minimal Inhibitory Concentration
Measured via
-MIC method
-Kirby-bauer method
-Antibiotic disks on agar plate