L4

Question 1

Requirement of a good antimicrobial?

Answer 1

Antimicrobials must act within the host without damaging the host (selective toxicity; “magic bullet”)

Question 2

What organism do antibiotics target

Answer 2

Bacteria

Question 3

Why are eukaryote pathogens more difficult to target for antimicrobials?

Answer 3

Eukaryote pathogens have cells more like our own so more difficult to treat cause not as much difference btwn pathogen cells and your cells.

Question 4

Describe the five main mechanisms of action of antibiotics on bacterial cells. Provide an example of each drug that uses each mechanism. Draw a diagram of a bacteria cell and indicate where each mechanism acts.

Answer 4

Slide 4

1. Inhibition of CELL WALL SYNTHESIS:
   - All bacteria have a cell wall, while human hosts do not. Its primary component is peptidoglycan.
   - E.g. Vancomycin
2. Inhibition of PROTEIN SYNTHESIS:
   E.g. Erythromycin
3. Inhibition of NUCLEIC ACID REPLICATION and TRANSCRIPTION:
   E.g. Rifampin
4. Injury to PLASMA MEMBRANE:
   - E.g. Polymyxin B
5. Inhibition of essential METABOLITE SYNTHESIS:
   - E.g. Trimethoprim

Question 5

What are the 3 ways antibiotics can block protein inhibition? Give an example of an antibiotic for each case.

Answer 5

1. Change shape of 30S portion, causing code on mRNA to be read incorrectly
   - E.g. Streptomycin
2. Bind to 50S portion and inhibits formation of peptide bond (sit near or in active site)
   - E.g. Chloramphenicol
3. Interfere with attachment of tRNA to mRNA-ribosome complex
   - E.g. Tetracyclines

Question 6

How does chemotherapy work

Answer 6

Using a compound that selectively targets and destroy abnormal or pathogenic cells (or viruses)

Question 7

What is an antiviral

Answer 7

Target different steps in viral replication

Question 8

What steps can an anti-viral target?

Answer 8

1. Inhibitors of fusion/entry of the virus to target host cell (e.g. block receptors on host cell that virus binds to)
2. Inhibit uncoating
3. Inhibit integration
4. Inhibit nucleic acid synthesis
5. Protease inhibitors
6. Exit/release inhibitors

Question 9

How do NUCLEOSIDE ANALOGS (Base + sugar) inhibit synthesis of viral DNA or RNA? Provide an example of one.

Answer 9

• Nucleoside analogs can shut down replication of viral DNA
• • In HSV infected cells, acyclovir impairs synthesis of viral DNA when it is incorporated into the 5’-3’ growing strand by DNA polymerase. Normally thymidine kinase phosphorylates nucleosides to form nucleotides to be incorporated into DNA by pol. In a healthy cell, TK recognizes non-nucleosides e.g. acyclovir, and will not phosphorylate them and will “ignore” acyclovir. But in virally infected cells, TK is altered and doesn’t recognize acyclovir as a non-nucleoside, which will then be phosphorylated and incorporated into growing strand of DNA. Acyclovir structurally resembles the nucleoside deoxyguanosine, but missing 3’OH. As it’s missing the 3’OH, no longer able to add another nucleotide and DNA synthesis is halted

Question 10

What is HAART?

Answer 10

• Highly active antiviral therapy
• Use combinations of drugs to minimize survival of resistant strains
• Usually 2 RT inhibitors and either a protease or integrase inhibitor in combo

Question 11

What are the 2 types of reverse transcriptase inhibitors? Give an example of each.

Answer 11

1. Nucleoside reverse transcriptase inhibitor (NRTIs)
   - Inhibits reverse transcriptase, preventing transcription of viral RNA into DNA
   - E.g. tenofovir
2. Non-nucleoside reverse transcriptase inhibitor (NNRTs)
   - Inhibits reverse transcriptase, preventing transcription of viral RNA into DNA
   - E.g. Efavirenz

Question 12

Fxn of integrase inhibitors? Example

Answer 12

• Inhibit HIV integrase that integrates cDNA into the host chromosome
• E.g. Raltegravir

Question 13

Fxn of protease inhibitors? Example

Answer 13

• Inhibit proteases that cleave viral precursor proteins into structural and functional proteins
• E.g. Indinavir

Question 14

Fxn of maturation inhibitors?

Answer 14

interfering with the maturation of the virus e.g. bind gag protein and disrupts its processing

Question 15

Fxn of tetherins?

Answer 15

Tether viruses to the cells, preventing their release and spread

Question 16

Example of

1) fusion/entry inhibitor
2) reverse transcriptase inhibitor
3) integrase inhibitor
4) protease inhibitor

Answer 16

1) fusion/entry inhibitor
- Maraviroc
2) reverse transcriptase inhibitor
- Tenofovir
3) integrase inhibitor
- Raltegravir
4) protease inhibitor
- Indinavir

Question 17

What are 4 ways bacteria cell can become antibiotic resistant

Answer 17

1. Blocking drug’s entry
2. Inactivation of drug by enzymes
3. Alteration of drug’s target molecule
4. Efflux of antibiotics

Question 18

Describe 5 misuses that lead to antibiotic resistance

Answer 18

1. Using outdated or weakened antibiotics
2. Using antibiotics for the common cold and other inappropriate conditions
3. Using antibiotics in animal feed (70%)
4. Failing to complete the prescribed regimen
5. Using someone else’s leftover prescription

Question 19

Why is the developed world particular prone to antibiotic resistance?

Answer 19

1. Antibiotics sold without prescriptions
2. 30% of antibiotic prescriptions for ear infections, 100% of antibiotic prescriptions for the common cold, and 50% of antibiotic prescriptions for sore throats are inappropriate or unnecessary (encouraging rise of resistant species