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Infection and Immunity > Antibacterial MoR > Flashcards

Antibacterial MoR Flashcards

1
Q

frequency of mutations

A

1 in every 10^6 - 10^8 cells

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2
Q

Government UK national action plan - 2019-2024

A

Reducing need for/unintentional exposure to antimicrobials
- Sanitation
- Water quality
- Farming practices

Optimising use of anti-microbials
- Diagnostic tests
- Surveillance
- Antibiotic stewardship

Investing in innovation, supply and access
- Profitability
- Vaccines
- Testing

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3
Q

Multi-drug resistance gram negative pathogens

A

Klebsiella pneumoniae - pneumonia/UTI

Pseudomonas aeruginosa - opportunistic infections

Escherichia coli - UTI/multiple infections

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4
Q

impact of resistant gram negative pathogens

A

account for 72% for all gram negative blood stream infections (BSIs) sepsis

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5
Q

which is the most common BSI

A

E. coli

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6
Q

what is XDR-TB?

A

Multi-drug resistant M. tuberculosis

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7
Q

Multi-drug resistance - plasmids

A

Transferred between bacteria by conjugation

can occur between different species = increases spread of antimicrobial resistance

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8
Q

conjugation

A

process by which one bacterium transfers genetic material to another through direct contact

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9
Q

echanisms of antimicrobial resistance

A
  1. Inactivate/modify drug
  2. Alter drug target
  3. Alter drug uptake/exit (i.e. transport)
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10
Q

beta-lactamases

A

enzymes produced by bacteria which hydrolyse β-lactams

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11
Q

4-classes of β-lactamases

A

A,C,D = serine at active site

B = metabollo-β-lactamases (Zn required)

Chromosomal or Plasmid-mediated

limited or extended spectrum

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12
Q

which plasmid-mediated β-lactamases are the most problematic?

A

plasmid mediated β-lactamases produced by gram negative bacteria

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13
Q

β-lactamases with Gram-positive bacteria

A

β-lactamase released from cell (excreted)

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14
Q

β-lactamases with Gram-negative bacteria

A

β-lactamase accumulate in periplasmic space

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15
Q

β-lactamase inhibitors

A

No antimicrobial activity but inhibit β-lactamases

extend use in clinic

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16
Q

β-lactamase insensitive

A

Addition of a sidechain inhibits some β-lactamase activity

17
Q

β-lactamase - altered target site

A

Beta-lactams target transpeptidase or penicillin-binding proteins (PBPs)
- Prevent cross-linking of peptides in
bacteria cell wall

Mutations in PBPs prevent β-lactams from binding

18
Q

Methicillin resistant Staphylococcus aureus (MRSA)

A

PBP2 -> PBP2a

MecA gene -> acquired new version of PBB2 gene on a transposon - inserts itself into chromosome

19
Q

what is MRSA resistant to?

A

all β-lactam antibiotics

20
Q

Resistance in haemophilus influenzae

A

PBP3 -> PBP3a + 3b

21
Q

Resistance in streptococcus pneumonia

A

PBP1 -> PBP1a + 1b

PBP2 -> PBP2a

22
Q

β-lactamase - altered uptake

A

gram negative bacteria only

reduced number/size of porins -> decreases permeability and prevents uptake

23
Q

Resistance to vancomycin - altered target site

A

Van A plasmid encoded resistance

Change in terminal amino acids of peptide chain

D-ala-D-ala (5 H bonds) -> D-ala-D-lactate (4 H bonds)

^ binding affinity reduced 100x

24
Q

Resistance to aminoglycosides - drug inactivation

A

Target ribosome

Aminoglycoside modifying enzymes

Usually plasmid encoded

25
Q

Types of aminoglycoside modifying enzymes

A
  1. Acetylases
  2. Phosphorylases
  3. Adenylases
26
Q

what are aminoglycoside modifying enzymes?

A

Catalyst the modification of aminoglycosides by addition of different groups at different positions

27
Q

Resistance to fluoroquinolones - altered target

A

Chromosomal mutations in DNA gyrase or topoisomerase IV

Inhibit binding of antibiotic to its target

28
Q

Resistance to tetracyclines - efflux pumps

A

[Expressed by gram positive/negative bacteria]

Actively pump substrates out of bacterial cell
- Tetracycline pump - resistance to single
antibiotic
- Inducible - switched on in presence of
tetracycline
- Plasmid encoded

29
Q

what has a large number of efflux pumps?

A

Pseudomanas

30
Q

mutation in efflux pumps

A

Chromosomally expressed

Basal expression confers intrinsic resistance

Mutation can cause upregulated expression confers acquired resistance

31
Q

2 classes of efflux pump associated with AMR

A
  • RND pumps expressed by gram negative bacteria (span across 2 membranes)

MFS pumps expressed by gram positive bacteria

32
Q

Chromosomal RND pump

A

Low level intrinsic resistance

Infection and Immunity (17 decks)

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