Lecture 34: Antibiotics Flashcards

1
Q

What is the use for the majority of antibiotics?

A

3/4 of the global antibiotic stock is in livestock

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2
Q

What types of infections are antibiotics used for? Why?

A

They are used only for bacterial infections, as they don’t work for viral infections.

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3
Q

What type of infections are the most dangerous today?

A

Lower respiratory infections.

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4
Q

What was the first antibiotic discovered?

A

Penicillin

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5
Q

How and by whom was penicillin discovered?

A

It was discovered by Sir Alexander Fleming. He discovered it by accident by leaving mold alone and noticing a clearing, which was caused by the release of penicillin.

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6
Q

Who isolated penicillin for the first time?

A

Sir Howard Florey and Ernst Chain

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7
Q

When and in what situation was penicillin first used?

A

It was first used after the Coconut Grove Fire in 1942. Penicillin was used to treat burn wounds.

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8
Q

How does the mode of discovery for streptomycin differ from the discovery of penicillin?

A

Unlike penicillin, which was accidental, streptomycin was the first antibiotic to be discovered systematically.

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9
Q

What bacterium produces stretomycin

A

It is produced by the soil bacterium Streptomyces griseus.

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10
Q

How was streptomycin discovered?

A

10,000 strains of soil bacteria and fungi were screened for antibacterial activity.

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11
Q

Who discovered streptomycin?

A

Selman Waksman

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12
Q

Were antibiotics invented or discovered? Explain why.

A

They were discovered, as they have produced naturally by bacteria for over 40 million years.

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13
Q

Why do bacteria naturally produce antibiotics?

A

Antibiotics are produced to counter competition from other bacteria - it is a fitness advantage.

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14
Q

What antibiotic class are Streptomycin?

A

Aminoglycosides

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15
Q

What is the difference between a bactericidal and a bacteriostatic antimicrobial?

A

A bacteriostatic antimicrobial halts reproduction and the population plateaus, while a bactericidal drug kills the population. However, this distinction is not absolute, as the dosage matters too.

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16
Q

Explain how bacteriostatic antibiotics work in general and give an example.

A

They interfere with a process that is required for cell replication. For example, inhibition of protein sythesis.

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17
Q

Explain how bactericidal antimicrobials work and give an example.

A

They interfere with processes required for cell survive. For example, lysis of the cell wall or DNA damage.

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18
Q

What is MIC?

A

Minimal inhibitory concentration. This is the minimal concentration of a bacteriostatic drug that inhibits the growth of a particular organism.

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19
Q

What does a high MIC indicate about a bacteria?

A

That it is highly resistant to the drug in question.

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20
Q

What are the 3 methods of determining the MIC of a bacteria to a particular agent?

A

Etest diffusion, Kirby Bauer disc diffusion, dilution susceptibility

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21
Q

How does the Etest diffusion test work?

A

A strip containing different concentrations of a given compound is applied to the plate with the bacterial culture. This measures the dose at which zones of clearing begin to form.

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22
Q

How does the Kirby Bauer disc diffusion test work?

A

Discs with the same concentrations of different compounds are placed into cultures to compare the zones of clearing.

23
Q

What does the size of the zone of clearing indicate about an antibiotic?

A

The larger the clearing, the more effective the antibiotic at a given concentration.

24
Q

How does the dilution susceptibility test work?

A

A liquid culture of bacteria is used, and different concentrations of antibiotics are added to different test tubes. It determines the concentration of antibiotic at which you start to see a clearing.

25
Q

What is the MBC?

A

The minimal concentration of a bactericidal drug that kills 99.9% of a particular organism.

26
Q

Explain how MBC is measured.

A

Starting at the MIC of the drug, do dilution assays while increasing the concentration. For each concentration, check if there are still any viable bacterial left when plated on agar. Once there are very few viable bacteria left the MBC has been reached.

27
Q

At the MIC vs at the MBC, compare the results in terms of viable bacteria and visible growth.

A

At the MIC, there is no visible growth, but there are still viable bacteria. At the MBC, there are very few viable bacteria left.

28
Q

Do all drugs have an MIC and an MBC? Explain.

A

All bactericidal drugs have an MBC and an MIC at a lower concentration. All bacteriostatic drugs have an MIC but not necessarily an MBC.

29
Q

Are MIC or MBC values typically used in clinical lab?

A

MIC is usually used and MBC is rarely used.

30
Q

What two qualities make a given feature of bacteria a good target for antibiotics?

A
  1. Must be essential to cellular function and structure
  2. Must be conserved across bacterial species and not shared in humans
31
Q

What are the 5 main types of antibiotics discussed?

A

Quinolones, beta-lactams, aminoglycosides, macrolides, tetracyclines

32
Q

What is the target of beta lactams?

A

The bacterial cell wall (peptidoglycan)

33
Q

Give 4 examples of beta lactams.

A

Penicillin, cephalosporins, monobactam, carbapenem

34
Q

Are beta lactams more effective in gram negative or gram positive bacteria? Explain why.

A

They are more effective in gram +, as gram - have the highly impermeable outer membrane that prevents many antibiotics from getting in.

35
Q

What are PBPs and what is their function normally?

A

PBPs are penicillin binding proteins. These are transpeptidases that are involved in the synthesis of peptidoglycan for cell wall biosynthesis. It needs to recognize the double amino acid sequence D-alanyl-D-alanine for binding.

36
Q

How do betalactams work as cell wall synthesis inhibitors?

A

They mimic the 3D structure of the dipeptide D-Ala-D-Ala component of peptidoglycans, as they share the ring structure. This will cause the cell to burst, as the PBPs will not be able to bind and the cell wall will not be synthesized correctly.

37
Q

Why is cell wall synthesis such a common target for antibiotics? When might they not be as effective?

A

It is conserved across many species and has multiple steps that can be inhibited by different types of compounds. However, these inhibitors are usually not active against gram-negatives because they can’t penetrate the outer membrane.

38
Q

What is the major target of antibiotics other than beta-lactams?

A

Prokaryotic protein synthesis.

39
Q

Which antibiotic target protein synthesis?

A

Tetracyclines, aminoglycosides, and macrolides

40
Q

How does the ribosome differ between prokaryotes and eukaryotes?

A

Prokaryotes: 70S ribosomes with 30S small subunit and 50S large subunit.
Eukaryotes: 80S ribosomes with 40S small subunit and 60S large subunit.

41
Q

Why are antibiotics that target protein synthesis able to be selective for bacteria and not humans?

A

Because the ribosomes of prokaryotes and eukaryotes have different structures, so they won’t affect mammalian protein synthesis and will have minimal side effects.

42
Q

What protein subunit do tetracyclines target?

A

They inhibit 30S

43
Q

What protein subunit do aminoglycosides target?

A

They inhibit 30S

44
Q

What protein subunit do macrolides target?

A

They inhibit 50S.

45
Q

What stage of protein synthesis do tetracyclines interrupt?

A

Initiation.

46
Q

What stage of protein synthesis do aminoglycosides interrupt?

A

Elongation

47
Q

What stage of protein synthesis do macrolides interrupt?

A

Termination

48
Q

Which antibiotic is this: one of the largest families with structurally varied compounds.

A

Aminoglycosides.

49
Q

Give 3 examples of animoglycosides.

A

Streptomycin, gentamicin, amikacin

50
Q

Are aminoglycosides bacteriostatic or bactericidal?

A

Bactericidal.

51
Q

What are the two likely mechanisms of action for aminoglycosides?

A
  1. Inhibits protein translocation
  2. Induces mistranslation leading to loss of cell wall integrity
52
Q

What types of organisms do aminoglycosides work on?

A

Gram negative and gram positives, but inactive against strict anaerobes.

53
Q

Are aminoglycosides commonly used? Explain why or why not.

A

No, their clinical use is very limited due to important side effects that are not yet fully understood.

54
Q

What are the 3 possible modes of delivery for antibiotics?

A

Oral, injectable, or intravenous