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Medical Microbiology > 5 + 6 Antibiotics > Flashcards

5 + 6 Antibiotics Flashcards

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Biology 101 flashcards USMLE® Step 1 flashcards
1
Q

Are antibiotics synthetic or naturally occurring?

A

Naturally occurring compounds

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2
Q

What do antibiotics show selective activity against? And what does it do?

A

Bacteria

Either kills bacteria or causes it to stop growing

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3
Q

What do antibiotics allow?

A

Treatment of infectious diseases

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4
Q

What criteria must be met for an antibiotic to be effective?

A

Target of antibiotic should be lacking in host tissue

Antibiotic becomes more concentrated in bacterial cells

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5
Q

How do antibiotics function? And what happens afterwards?

A

Bind to specific target enzymes or molecules within bacterial cell
Nothing- there are no secondary effects

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6
Q

What do antibiotics inhibit the syntheses of?

A

Important macromolecules

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7
Q

How are antibiotics classified? What are the 3 categories of antibiotics?

A

According to the type of macromolecule they inhibit the synthesis of

  1. Nucleic acid synthesis - DNA or RNA
  2. Protein synthesis - often translational apparatus
  3. Peptidoglycan synthesis - affects cell wall development
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8
Q

What do antibiotics interfering with DNA or RNA synthesis do?

A

Block nucleotide production

Inhibit enzymes catalysing synthesis (Eg. DNA gyrase and RNA polymerase)

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9
Q

How can nucleotide production be prevented?

A

Nucleotide synthesis is due to a series of steps within a pathway. Blockage of any of these steps prevent nucleotide synthesis

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10
Q

What are 2 examples of nucleotide synthesis steps that can be blocked?

A

Conversion of PABA to DHPA

Conversion of DHFA to THFA

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11
Q

What does THFA stand for? And what is it?

A

Tetrahydrofolate is a precursor for purine and pyrimidine synthesis

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12
Q

What two types of synthetic antibiotics inhibit tetrahydrofolate?

A

Sulphonamides and trimethoprim

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13
Q

What are sulphonamides and what are they used for?

A

Structural analogues of p-aminobenzoic acid

Act as alternative substrates for dihydropteroate synthase (DHPS)

Blocks enzymes function

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14
Q

What is trimethoprim an analogue of and what does it inhibit and prevent?

A

Analogue of dihydrofolate
Inhibits dihydrofolate reductase
Prevents THFA synthesis

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15
Q

What is trimethoprim used to treat?

A

Uncomplicated UTIs caused by Gram negatives

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16
Q

What can Co-trimoxazole be used for?

A

Pyelonephritis (kidney) and prostatitis (prostate)

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17
Q

Describe the structure of a bacterial cell genome.

A

Is a closed, circulare, double stranded DNA molecule

Normally a supercoiled structure

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18
Q

What must happen to the DNA strands in order for replication to occur?

A

Strands must be separated

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19
Q

Explain DNA supercoiling.

A

Positive supercoiling occurs downstream of ori (origin of replication) site

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20
Q

What happens if DNA doesnt relax?

A

No more unwinding occurs

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21
Q

What does DNA gyrase do?

A

An enzyme which relaxes supercoiling and breaks phosphodiester bonds in both strands

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22
Q

Do bonds reform after relaxing?

A

Yes

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23
Q

What happens when the action of DNA gyrase is impeded?

A

DNA replication stops which results in no cell division

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24
Q

Which antibiotics inhibit DNA gyrase? And name an example.

A

Quinolone.

An example of such is naladixic acid

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25
Q

What has happened to quinolone antibiotics recently?

A

2nd generation been developed

Ciproflaxacin is an example

Introduces a broader spectrum of activity

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26
Q

What does RNA polymerase do?

A

Catalyses the transcription of RNA polymerase

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27
Q

Which group of antibiotics blocks RNA polymerase activity? And give an example

A

Rifamycin

Example is rifampicin

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28
Q

What sort of infections do rifamycin antibiotics treat?

A

Many Gram positive infections

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29
Q

Which stages of protein synthesis are effected by their inhibitors?

A

Elongation and initiation

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30
Q

Name 5 different categories of antibodies that exist to inhibit protein synthesis

A 
Aminoglycosides
Tetracyclines
Macrolides
Amphenicols
Oxazolidinones
31
Q

Give an example of an aminoglycoside and what it does.

A

Streptomyocin is bactericidal (bacteria killing)

It is irreversibly bound at single site in 30S ribosomal subunit and blocks the formation of 30S initiation complex needed for protein synthesis to start

32
Q

Another example of an aminoglycoside is Spectinomycin. What does it do? Is the action reversible?

A

Inhibits the elongation stage and binds to the 30S subunit

Inhibits the normal translocation (movement) of ribosome along mRNA molecule

Action is reversible and bacteriostatic

33
Q

What does gentamycin (aminoglycoside) do?

A

Binds irreversibly at multiple sites in ribosomes
Bactericidal
Inhibits the elongation stage

34
Q

How does gentamycin stop elongation?

A

Elongation is stopped by preventing the binding of elongation factor (EF-G) to ribosome

35
Q

What are two antibiotics that have similar modes of action to gentamycin?

A

Tobramycin and neomycin

36
Q

What sort of infections are aminoglycosides used for?

A

Infections with Gram negative aerobes eg coliforms

37
Q

What sort of antibiotic are tetracyclines?

A

Bacteriostatic antibiotics which display a broad spectrum of activity

38
Q

Why is the use of tetracyclines limited?

A

Spread of resistance

39
Q

What sort of pathogens are tetracyclines used for?

A

Obligate intracellular eg Chlamydia trachomatis

40
Q

Where do tetracyclines bind? And is it reversible?

A

Bind reversibly to the site in 30S subunit

41
Q

What do tetracyclines disrupt?

A

Disrupt the codon-anticodon interaction between mRNA and tRNA

42
Q

What has the development of glycylcyclines allowed us to overcome?

A

The problems the tetracyclines have with resistance

43
Q

How do macrolides function?

A

Binding to specific site in 50S ribosomal subunit

44
Q

What does the binding of macrolides do?

A

Stimulates premature dissociation of peptidyl tRNA from ribosomes during protein synthesis

45
Q

What are macrolides used to treat? And give some examples of types of macrolides

A

Gram positive cocci

Erythromycin and clarithromycin

46
Q

What do amphenicols inhibit?

A

Inhibiting peptidyl transferase which is a ribosomal enzyme catalysing peptide bond formation

47
Q

What do amphenicols bind to?

A

They bind to a specific site on 50S ribosomal subunit

48
Q

Where are amphenicols used and what are they effective against?

A

Used in eye drops and effective agains E.coli, S.aureus and streptococcus pneumonia

49
Q

Where do oxazolidinones attach to?

A

50S subunit and block the formation of 70S initiation complex

50
Q

What are oxazolidinones used for?

A

Gram positive cocci

Methicillin-resistant Staphylococcus aureus (MRSA)
Vancomycin-resistant Enterococcus (VRE)

51
Q

For what reason are bacterial cells susceptible to lysis?

A

They are unable to synthesise peptidoglycan

52
Q

Why are antibiotics that inhibit peptidoglycan synthesis ideal?

A

Human cells contain no peptidoglycan whereas almost all bacterial cells do

53
Q

Antibiotics that inhibit peptidoglycan synthesis are ideal at doing what?

A

Killing bacteria

54
Q

How many steps are there to peptidoglycan synthesis?

A

3 major steps

55
Q

Where does the first stage of peptidoglycan synthesis occur and what happens?

A

Occurs in the cytoplasm

UDP-NAMA-pentapeptide precursors are prepared

56
Q

What happens in the second stage of protein synthesis?

A

Involves the transmembrane movement if the precursor (and addition of NAG) to the outer membrane surface

57
Q

What happens in the last stage of protein synthesis?

A

Incorporation of NAG-NAMA-tetrapeptide into growing peptidoglycan

58
Q

What does fosfomycin do during stage 1 of peptidoglycan synthesis? And what is it used to treat?

A

inactivates pyruvyl transferase which blocks the formation of intermediate UDP-NAG-enoylpyruvate
Mainly used for treatment of UTIs

59
Q

What is fosfomycin an analogue of?

A

PEP

60
Q

What is D-cycloserine an analogue of?

A

D-alanine

61
Q

How does D-cycloserine act as a stage 1 inhibitor of peptidoglycan synthesis?

A

Inhibits alanine racemase and D-alanyl-D-alanine synthetase which blocks synthesis of D-alanyl-D-alanine

62
Q

What is D-cycloserine used to treat?

A

Second line treatment for TB

63
Q

What does Bacitracin do as a stage 2 inhibitor of peptidoglycan synthesis?

A

The cyclic polypeptide blocks the membrane transport phase of synthesis by binding to undecaprenyl pyrophosphate (lipid carrier)

64
Q

What does bacitracin do to the lipid carrier?

A

Prevents enzymatic dephosphorylation of lipid carrier to monophosphate form. Dephosphorylation is is essential the carrier to bind UDP-NAMA-pentapeptide

65
Q

What is bacitracin used to treat?

A

Used with neomycin and polymyxin B for skin or eye infections

66
Q

What sort of peptides inhibit stage 3 peptidoglycan synthesis? And give an example

A

Glycopeptides an example is vancomycin

67
Q

What is the transglycosylation process?

A

Causing insertion of NAG-NAMA-pentapeptide unit into growing peptidoglycan chain

68
Q

What do glycopeptides do during peptidoglycan synthesis?

A

Blocks the transglycosylation process by binding to both the incoming unit and the exposed D-alanyl-D-alanine end of growing peptidoglycan chain

69
Q

What is it about vanomycin that makes it a last resort for treatment and what is it used to treat?

A

Toxicity means it is a last resort for serious infections caused by Gram positive species

70
Q

What does televancin do?

A

Acts in the same way as vanomycin, also causes membrane depolarisation

71
Q

What sort of antibiotic are in the category of β-lactams?

A

Penicillin (penams) and cephalosporin (cephems)

72
Q

What sort of bacteria are β-lactams effective against?

A

Both Gram positive and negative

73
Q

What are β-lactams analogues of?

A

D-alanyl-D-alanine

74
Q

How do β-lactams work? Which results in what?

A

They inhibit the final stage (transpeptidation reaction)
The transpeptidase enzyme recognises antibiotic instead of substrate which results in transpeptidase cleaving β-lactam ring

Medical Microbiology (9 decks)

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