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BS131: Health & the Community > Lecture 9. Mode of Action > Flashcards

Lecture 9. Mode of Action Flashcards

1
Q

What are biofilms?

A

An assembly of microbial cells associated with a surface, and enclosed in an extracellular matrix made principally of polysaccharides

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2
Q

What are biofilm-associated organisms fundamentally different from?

A

Populations of suspended (planktonic) cells

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3
Q

What does the formation of biofilms allow bacteria to become?

A

Tolerant to antibiotics/antimicrobials, and generates resistance

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4
Q

What does slow diffusion lead to?

A

Tolerance

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5
Q

What do sublethal concentrations of antimicrobials in the biofilm lead to?

A

Selection of antimicrobial resistance (AMR)

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6
Q

What is the antibiotic resistance mechanism in Gram-negative bacteria?

A

Intrinsic - have a double-membrane structure that makes the cellular envelope relatively impermeable

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7
Q

What is the antibiotic resistance mechanism in Gram-positive bacteria?

A

Acquired - Alterations to envelope structure, such as porin loss reduce permeability to antibiotics leading to acquired antibiotic resistance

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8
Q

What are two examples of non-specific antibiotic resistance mechanisms?

A

Porins and efflux pumps

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9
Q

What do efflux pumps do?

A

Decrease the concentration of antibiotic within the cell

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10
Q

What antibiotics target cell wall synthesis?

A

Penicillins
Cephalosporins
Carbapenems
Monobactams

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11
Q

What antibiotics target nucleic acid synthesis?

A

Quinolones

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12
Q

What antibiotics target the 30S subunit in the ribosome?

A

Amicoglycosides
Tetracyclines

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13
Q

What antibiotics target the 50S subunit in the ribosome?

A

Macrolides
Chloramphenicol

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14
Q

What is a β-lactam antibiotic?

A

A member of a large group of broad-spectrum agents related to β-lactam

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15
Q

What do most β-lactam antibiotics target?

A

Penicillin-binding proteins

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16
Q

What are penicillin-binding proteins?

A

Penicillin-binding proteins (PBPs) are DD-transpeptidases that make cross-links (peptide bonds) between D-amino acid residues in sugar-lined pentapeptides in the bacterial cell walls
Essential for bacterial cell wall synthesis

17
Q

How do β-lactam antibiotics work?

A

The reactive β-lactam ring binds the active site of the transpeptidase, permanently inactivating D-alanine the PBP: cell wall cross-linking ceases

18
Q

What are the four ways resistance to β-lactam antibiotics can occur?

A
  1. Mutation of PBP, lowering the affinity for penicillins, etc
  2. Down-regulation of porins in Gram-negative bacteria
  3. Acquisition of β-lactamase- ESBL (extended spectrum β-lactamase)
  4. Up-regulation of efflux pumps
19
Q

What are quinolone antibiotics?

A

A member of a large group of broad-spectrum bacteriocidals that share a bicyclic core structure related to the compound 4-quinolone

20
Q

What do quinolone antibiotics target?

A

Topoisomerase

21
Q

What do type II topoisomerases convert?

A

Positive supercoils (over-wound) into negative supercoils (under-wound)

22
Q

What do topoisomerases regulate?

A

Supercoiling in DNA synthesis and RNA synthesis

23
Q

What do gyrase and topoisomerase IV both consist of?

A

Two A subunits and two B subuints

24
Q

What does the B subunit do?

A

Carries out the nicking of DNA

25
Q

What does the A subunit do?

A

Introduces negative supercoils, and then reseals and ligates the strands

26
Q

How do ciprofloxacin (and other quinolone antibiotics) work?

A

Quinolones act by converting their targets, type II topoisomerases (gyrase and topoisomerase IV), into toxic enzymes that fragment the bacterial chromosome
These double stranded cuts are hard to repair
Ultimately they cause bacterial cell death

27
Q

What are the four ways resistance to quinolones can occur?

A
  1. Mutation in gyrase and topo IV weaken quinolone-enzyme interactions
  2. Plasmid – encoded Qnr proteins decrease topoisomerase–DNA binding
  3. A plasmid - encoded enzyme acetylates ciprofloxacin decreasing its effectiveness
  4. Plasmid-encoded efflux pumps decrease the concentration of quinolones in the cell
28
Q

What are aminoglycoside antibiotics?

A

Contains amino-sugar structures

29
Q

What do aminoglycoside antibiotics inhibit?

A

Protein synthesis

30
Q

What do aminoglycoside antibiotics display bactericidal activity against?

A

Gram-negative aerobes but generally not against anaerobic Gram-negative bacteria

31
Q

How do aminoglycoside antibiotics work?

A

Aminoglycosides inhibit protein synthesis by high affinity binding to the A-site on the 16S ribosomal RNA of the 30S ribosome

32
Q

How does binding to the A site cause problems?

A

Aminoglycoside binding to the 30S subunit of the ribosome causes codon misreading. This leads to misincorporation of amino acids into elongating peptides – error prone protein synthesis

33
Q

What can modify aminoglycosides?

A

Acetyltransferases

BS131: Health & the Community (23 decks)

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