Anti-Bacterials - Protein Synthesis Flashcards

1
Q

Name some antibacterial agents that target protein synthesis.

A

Aminoglycosides, tetracyclines, chloramphenicol, macrolides, oxazolidinones, fusidic acid.

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2
Q

How many proteins make up the bacterial ribosome?

A

Over 30.

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3
Q

Describe the four phases of bacterial protein synthesis.

A

Initiation, elongation, termination, ribosome recycling.

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4
Q

Which way is the mRNA translated?

A

5’-3’.

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5
Q

What are the ribosome sub-units required in the translation of mRNA?

A

30S and 50S.

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6
Q

What are the three initiation factors required in the translation of mRNA?

A

JF1, JF2 (GTP), JF3.

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7
Q

What is the initiator required in the translation of mRNA?

A

f-Met-tRNA-f-Met.

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8
Q

What does f-Met relate to?

A

N-formylmethionine.

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9
Q

What are the elongation factors required in the translation of mRNA?

A

EF-Tu (GTP), EF-Ts, EF-G.

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10
Q

What phase of bacterial protein synthesis do Oxazolidiones act upon?

A

Initiation.

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11
Q

What does IF3 do in bacterial protein synthesis?

A

It binds to the 30S subunit in the initiation phase, promoting dissociation of the ribosome into its two subunits and allowing 30S to form an initiation complex.

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12
Q

Where does IF1 bind in the initiation phase of bacterial protein synthesis? What effect does this have?

A

The base of the A-site of the 30S ribosomal subunit. This directs the initiator tRNA to the ribosomal P-site by blocking the A-site.

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13
Q

What does IF2 do in bacterial protein synthesis?

A

IF-2 is a small GTP-binding protein. IF-2-DTP bonds the initiator fMet-tRNAfMet and helps it dock with the small ribosomal subunit.

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14
Q

How is the initiation complex completed?

A

IF-2-GTP hydrolysed and IF3 released and 50S subunit binds.

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15
Q

Describe the oxazolidinone nucleus.

A

A 5-membered ring with a carbonyl group on in the top position, an oxygen to its right, and a nitrogen to its left.

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16
Q

How can the properties of oxazolidinones be altered?

A

By altering the chains on wither side of the nucleus.

17
Q

What classes of drugs act upon the elongation phase of bacterial protein synthesis?

A

Aminoglycosides, Tetracyclines.

18
Q

What happens when the fMet-tRNA enters the P-site?

A

It causes a conformational change which opens the A-site for the new aminoacyl-tRNA to bind to the codon.

19
Q

What brings aminoacyl-tRNA into the ribosomal A-site.

A

EF-Tu.

20
Q

What is transpeptidation?

A

The amino acid at P-site is transferred to the amino acid at A-sit of the growing peptide chain.

21
Q

How do aminoglycosides work to inhibit bacterial protein synthesis?

A

Some aminoglycosides change the shape of the 30S subunit, leading to misreading of the mRNA – the detailed mechanism of this process is unknown.

22
Q

Name some aminoglycosides.

A

Streptomycin, gentamycin.

23
Q

How do tetracyclines work to inhibit bacterial protein synthesis?

A

Some tetracyclines (and some aminoglycosides) prevent amino acids from entering the ribosome at the 30S subunit. The detailed mechanism of this process is unknown.

24
Q

Name some tetracyclines.

A

Tetracycline, doxycycline, minocycline.

25
Q

Describe the tetracycline nucleus.

A

A group of four 6 membered rings.

26
Q

What bacteria is tigecycline effective against? What resistance mechanism is it partially resistant to?

A

Tigecycline is effective against; MRSA, VRA, many G -ive bacteria and is partially resistant to the efflux mechanism of resistance.

27
Q

When is tigecycline used?

A

Only sparingly when needed.

28
Q

Why shouldn’t tetracycline be given to pregnant mothers or children under 8?

A

Tetracycline binds very tightly to calcium, becoming deposited in calcifying tissues such as bones and teeth, causing staining and slight weakness.

29
Q

What food/drink should tetracyclines not be given with? Why?

A

Milk, because they bind tightly to calcium.

30
Q

Describe transpeptidation.

A

The peptide bond formation involves nucleophilic attack of the amino N of the amino acid that is linked to the 3’ hydroxyl of the terminal adenosine of the tRNA in the A-site on the carbonyl C of the amino acid (with attached nascent polypeptide) in ester linkage to the tRNA in the P-site.

31
Q

What classes of drugs inhibit the transpeptidation phase of bacterial protein synthesis?

A

Puromycin, Chloramphenicol, Kanamycin (aminoglycoside), kirromycin.

32
Q

How does puromycin act to inhibit the transpeptidation of bacterial protein synthesis?

A

Puromycin causes premature chain termination. It resembles the aminoacyl-tRNA, it has an ‘NH’ instead of the ‘O’ that joins the amino acid to tRNA. This stronger amide bond is not reactive enough and the new peptide bond forms too slowly. Hence, the ribosome stalls or an incomplete chain is released.

33
Q

What issue causes puromycin to be only used in cell culture?

A

Unfortunately, this drug has poor selectivity between prokaryotic and eukaryotic cells so is mainly used in cell culture.

34
Q

Which form of chloramphenicol is pharmacologically active?

A

D-threo.

35
Q

How does chloramphenicol act to inhibit the transpeptidation phase of bacterial protein synthesis?

A

It has a selective action on peptidyl transferase of the 50S subunit, blocking peptide bond formation.

36
Q

Why is chloramphenicol the drug of choice for treating typhoid and meningococcal meningitis?

A

Chloramphenicol penetrates mammalian cells and CSF.

37
Q

How does kanamycin act to inhibit the transpeptidation phase of bacterial protein synthesis?

A

Kanamycin causes a misreading of the code by interfering with the (wobble) base paring. It doesn’t prevent the reaction, it prevents proper binding, causing the wrong tRNA to bind which inactivates the protein.

38
Q

What is the consequence of the production of incorrect proteins?

A

This production of incorrect proteins means the cell has to destroy these proteins and make new ones, which takes a lot of energy. This eventually kills the cell through energetic depletion.

39
Q

How does kirromycin act to prevent the transpeptidation phase of bacterial protein synthesis?

A

Kirromycin blocks dissociation of GDP from EF-Tu after hydrolysis. This prevents dissociation of EF-Tu from the ribosome and effectively stalls protein synthesis.