2.2.1. Intro to Antibiotics

Question 1

Why are bacteria susceptible to sulfa drugs?

Answer 1

Unlike body cells, that can benefit from preformed folic acid in the environment, bacteria that make folic acid lack a system for its uptake and are susceptible to sulfonamides (inhibit the synthesis of folic acid, but not its utilization)

Question 2

Antibiotics

Answer 2

An antimicrobial agent of microbial origin with a low molecular weight and a specific spectrum of activity (broad versus narrow)

Question 3

Bactericidal agents

Answer 3

Are lethal (may or may not cause cell lysis) and, in general, are only effective against growing cells

Example: penicillin

Question 4

Bacteriostatic agents

Answer 4

Reversibly inhibit bacterial growth and often resemble metabolite analogs (act as competitive inhibitors)

Question 5

In what circumstances are bactericidal drugs preferred?

Answer 5

When the body’s defenses are insufficient to clear the invading agents

Question 6

Reasons for Selective Toxicity

Answer 6

1. Absence of the target from the host
2. Permeability differences
3. Structural differences in the target

Question 7

Vancomysin

Answer 7

Targets peptidoglycan

Question 8

B-lactam antibiotics

Answer 8

Best example is penicillin, which affects the biosynthesis of the murein layer of the bacterial cell wall

Question 9

Reason for Gentamicin’s selective toxicity

Answer 9

Not affectively taken up by host cells

Question 10

Reason for Chloramphenicol’s selective toxicity

Answer 10

Targets bacterial 50S ribosomal subunit but not host 60S

Question 11

Selective Pressure

Answer 11

The process by which treatment with antibiotic selects for those bacteria that have acquired resistance. Exact reason that we do not over treat with antiobiotics

Question 12

Sulfonamides

Answer 12

Broad spectrum bacteriostatic drugs that act as inhibitors of folic acid (starving the bacteria of bases necessary for DNA replication and transcription)

Question 13

Trimethoprim

Answer 13

Prevents bacteria from using folic acid to form nucleotides

Question 14

Methotrexate (MTX), trimethoprim (TMP), and pyrimethanmine

Answer 14

Inhibit dihydrofolate reductase in humans, bacteria, and protozoa (prevents utilization of folic acid). Exhibit selective toxicity (more toxic in protozoa and bacteria than humans).

Lead to decreased levels of dTMP, a mononucleotide

Question 15

Para-Amino Salicylic Acid is effective against…

Answer 15

Effective against TB

Question 16

Describe Rifampin and Rifabutin

Answer 16

• Bactericidal
• Narrow spectrum (strep, staph, neisseria, mycobacteria)
• Bind to beta subunit of RNA polymerase, inhibiting initiation of transcription

Question 17

What is the common feature of drugs with the suffix -azole?

Answer 17

ergosterol synthesis inhibitor (e.g., Ketoconazole)

Question 18

What is the common feature of drugs with the suffix -bendazole?

Answer 18

antiparasitic/antihelmintic [parasitic worms] (e.g., Mebendazole)

Question 19

What is the common feature of drugs with the suffix -cillin?

Answer 19

peptidoglycan synthesis inhibitor (e.g., Ampicillin)

Question 20

What is the common feature of drugs with the suffix -cycline ?

Answer 20

protein synthesis inhibitor (e.g., Tetracycline)

Question 21

What is the common feature of drugs with the suffix -ivir?

Answer 21

neuraminidase inhibitor (e.g., Oseltamivir)

viral neuraminidase is responsible for the spread of the influenza virus

Question 22

What is the common feature of drugs with the suffix -navir?

Answer 22

protease inhibitor (e.g., Ritonavir)

Question 23

What is the common feature of drugs with the suffix -ovir?

Answer 23

DNA polymerase inhibitor (e.g., Acyclovir)

Question 24

What is the common feature of drugs with the suffix -thromycin?

Answer 24

macrolide [ring structure] antibiotic (e.g., Azithromycin)

Question 25

Describe Metronidazole

Answer 25

1. disrupts DNA structure, inhibits DNA replication, and causes DNA breaks and secondary mutations
2. pro-drug
3. narrow spectrum against anaerobic infections

Question 26

Resistance to metronidazole is caused by…

Answer 26

Mutations in the oxidoreductases that affect pro-drug conversion

Question 27

Describe Quinolones

Answer 27

1. Bactericidal Drugs

2. Act by inhibiting the action of bacterial topoisomerases, including DNA gyrase (G+) and topoisomerase IV (G-)

Question 28

Nalidixic acid is used for…

Answer 28

used to treat UTI

Question 29

Fluroquinolone is used for …

Answer 29

used to treat G+ and G-

Question 30

Resistance to Quinolones is caused by…

Answer 30

1. Mutations in the genes encoding the target enzymes DNA gyrase and topoisomerase IV (i.e., reduced binding)
2. Efflux pumps

Question 31

Describe the B-lactam antiobiotic pathway…

Answer 31

1. Association w/ bacteria
2. Penetration through outer membrane (G-)
3. Interaction w/ PBPs
4. Activation of an autolysin that degrades the cell wall

Question 32

Resistance to B-lactam is caused by…

Answer 32

G+ produce extracellular B-lactamases that destroy the antibiotic before it comes into contact with the bacterial surface

Question 33

Describe Daptomycin

Answer 33

A lipopeptide antibiotic that binds to the cell membrane of G+ and forms a disruptive ion channel that causes depolarization and rapid cell death

Question 34

Oxazolidinones bind…

Answer 34

Bind the 50S subunit of bacterial ribosomes (entirely synthetic)

Question 35

How do Polymyxins work?

Answer 35

Hydrophobic tail inserts into the cell membrane (head binds to PE and LPS) and disrupts the cell membranes of gram (-) bacteria

Question 36

Resistance to Polymyxins is caused by…

Answer 36

G- bacteria have a structural modification of the lipid A moiety of LPS

Question 37

Aminoglycosides work through…

Answer 37

Penetration of the outer membrane of G-, association with a two-stage active transport system, and binding to the 30S ribosomal subunit

Question 38

Factors limiting successful chemotherapy

Answer 38

1. Failure of the drug to enter the host cell (location)
2. Abscess formation and necrosis
3. Presence of foreign bodies

Question 39

Types of resistance

Answer 39

1. Intrinsic (e.g., mycoplasma does not have peptidoglycan so Vancomycin would not work)
2. Acquired (horizontal gene transfer or spontaneous mutation)
3. Selective pressure

Question 40

Describe synergism between sulfa drugs and trimethoprim

Answer 40

Both drugs act on metabolism, but their sites of action are different (resistance to one does not mean resistance to both). Trimethoprim blocks the function rather than the synthesis of folic acid by inhibiting dihydrofolate reductase

Question 41

Drug interactions

Answer 41

1. Synergism (bactericidal + bactericidal)
2. Antagonism (bactericidal + bacteriostatic)
3. Indifference

Question 42

Describe Tetracycline and Penicillin interaction

Answer 42

Antagonism: tetracycline blocks protein synthesis, preventing the cell growth required for penicillin to cause lysis

Question 43

Plate Dilution Assay

Answer 43

Allows you to determine MIC (Minimal Inhibitory Concentration, lowest concentration of a drug that inhibits more than 99% of bacterial cells)
Can test several bacterial isolates at once

Question 44

Tube Dilution Assay

Answer 44

Advantage: may plate the bacteria afterwards to see if the drug is bactericidal or bacteriostatic
Disadvantage: requires lots of tubes

Question 45

Broth Microdilution Assay

Answer 45

Miniaturized version of the tube dilution assay

Advantage: may test a single bacterial isolate against a wide range of drugs to find multiple MIC’s

Question 46

Disc Diffusion Method

Answer 46

Plate bacteria onto an agar plate, then place discs with antibiotic on them (CANNOT tell whether antibiotic is bacteriostatic or bactericidal)