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Infection and Immunity > Antibacterial MoA > Flashcards

Antibacterial MoA Flashcards

1
Q

Antimicrobial

A

any chemicals which kill or inhibit microbial growth in or on a body surface (fungal, viral, bacteria)

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2
Q

Antibacterial

A

any chemical which specifically targets bacteria or kills/inhibits its growth

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3
Q

Antibiotic

A

drug used to treat bacterial infections

Synthesised by a microorganism and selectively inhibit/kills off another microorganism

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4
Q

Sources of antibiotics

A

Micro-organism -> e.g. penicillin

Synthesis -> e.g. chloramphenicol

Semi-synthesis (most common) -> amoxicillin

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5
Q

Selective toxicity

A

selectively kills or inhibits target organism whilst causing no or minimal harm to host

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6
Q

Bacteriostatic

A

slow down or stall bacterial growth

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7
Q

Bactericidal

A

kill bacterial

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8
Q

Ideal properties of anti-bacterials

A

Specific - ability of drug/chemical agent to interact with defined target

Selective - selectively kills or inhibits the target organism, whilst causing no or minimal harm to host

Bactericidal

Minimal emergence of resistance to the drug

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9
Q

Ideal activities of anti-bacterials

A

Non toxic to host

Long plasma half-life

Good tissue distribution

Low plasma protein binding

Oral and parenteral

No interference with other drugs

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10
Q

Inhibitors of cell wall synthesis

A

B lactams - penicillins, cephalosporins, carbapenems, monobactams

Glycopeptides - vancomycin, teicoplanin

Isoniazid

Fosfomycin

Cycloserine

Bacitracin

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11
Q

cell walls of gram positive bacteria

A

Thin peptidoglycan layer

outer membrane

contains lipopolysaccharides

porin channels

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12
Q

cell walls of gram negative bacteria

A

thick peptidoglycan layer

no outer membrane

contains techoic acids and lipotechoic acids

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13
Q

β-Lactams

A

[inhibitors of cell wall synthesis]

All contain β-Lactam ring

Differences in structure of ring attached to β-Lactam and side chains (R-group)

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14
Q

β-Lactam - main direct MoA

A

Bind and inhibit action of penicillin binding proteins (PBPs), also known as transpeptidases

Prevents cross-linking

Lose rigidity of cell wall in the vertical direction -> cell lysis

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15
Q

β-Lactam - direct MoA 2

A

Structure similar to last 2 amino acids on side chain

Get incorporated into peptide side chain

Prevents cross-linking + affects rigidity of cell wall -> cell lysis

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16
Q

β-Lactam - Indirect MoA

A

Presence of β-Lactam stimulates production of autolysins (= enzyme that causes bacteria to break down their own cell wall)
= cell lysis

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17
Q

what type of bacteria do glycopeptides act on?

A

gram positive

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18
Q

glycopeptide - target

A

binds to terminal d-ala

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19
Q

glycopeptide - MoA

A

D-ala on peptide side chain of peptidoglycan monomer-terminal amino acid can’t be removed

Prevents cross-linking of peptide side chains

Prevents glycosylase enzyme from adding PG monomer on PG chain

20
Q

why do large molecules work on outer surface of cytoplasmic membrane

A

can’t penetrate cytoplasmic membrane

21
Q

what type of bacteria do polymyxins act on?

A

gram negative

22
Q

polymyxins - MoA

A

Binds to lipid A

Distorts membrane

Penetrates cell wall

Disrupts membrane integrity

Allows leakage of cytoplasmic contents

23
Q

which inhibitors act on cell membrane?

A

Polymyxins and Lipopeptides

24
Q

how do antimicrobials act on nucleic acids?

A

Metabolic inhibitors of NA synthesis - inhibit synthesis of nucleic acid precursors
- Sulfonamides
- Trimethoprim

Affect RNA polymerase - disrupts RNA production
- Rifamycins

Affect DNA directly - e.g. may cause strand breakage
- Nitroimidazoles

Affect DNA replication - e.g. strand breakage
Fluoroquinolones

25
Q

DNA replication - stage 1

A

DNA replication starts at origin

dsDNA unwound by helicase to expose template DNA strands

Unwinding generates supercoils which are removed by DNA gyrase (topoisomerase II)

26
Q

DNA replication - stage 2

A

Zone of unwound DNA = replication fork

DNA polymerase syntheses complimentary

DNA strands at replication fork
Replication = bidirectional

27
Q

DNA replication - stage 3

A

2 replication forks collide at opposite side of chromosome

2 circular chromosomes now linked together

Topoisomerase IV separates DNA
Chromosomes partitioned into each daughter cell

28
Q

what does DNA gyrase do?

A

removes DNA supercoils ahead of replication fork

29
Q

what does topoisomerase IV

A

separates DNA after replication

30
Q

Fluoroquinolones - MoA

A

Bind and inhibit DNA gyrase AND/OR type IV topoisomerases when complexed with bacterial DNA

This inhibits DNA replication and packaging of DNA -> cell lysis

31
Q

bacterial ribosomes

A

[50S subunit]

-23S rRNA
-5S rRNA
-proteins

[30S subunit]

-16S rRNA
-proteins

32
Q

mammalian ribosomes

A

[60S subunit]

-26S rRNA
-5S rRNA
-proteins

[40S subunit]

-18S rRNA
-proteins

33
Q

significance of differences in ribosomal structure

A

provide selective inhibition of bacterial protein synthesis

34
Q

translation - initiation

A

Ribosome assembles around the template mRNA

First tRNA is attached at the start codon

35
Q

translation - elongation

A

tRNA transfers an amino acid to the mRNA corresponding to the next codon

Ribosome then moves (translocates) to next mRNA codon to continue process, creating an amino acid chain

36
Q

translation - termination

A

When stop codon is reached, ribosome releases polypeptide

37
Q

Tetracyclines - MoA

A

Binds reversibly to A site on 16S rRNA in 30S subunit

Inhibits binding of tRNA to A-site

Inhibits protein synthesis

38
Q

Tetracyclines - binding in bacterial vs mammalian ribosomes

A

Binds effectively to mammalian ribosome (side effects)

Selectively through better binding to bacterial ribosome and better accumulation of antibiotic inside bacterial cell

39
Q

what type of antibiotic are tetracyclines?

A

reversible

bacteriostatic

40
Q

Aminoglycosides - MoA

A

[Bind irreversibly to A-site on 16S rRNA in 30S subunit]

  1. Inhibit binding of tRNA to A-site
  2. Prevent formation of initiation complex
  3. Cause misreading of codons along mRNA
  4. Increase membrane permeability -> increased accumulation in cell
41
Q

what type of antibiotic are aminoglycosides?

A

irreversible

bactericidal

42
Q

antibacterials - site of action - CELL WALL

A

major target

unique to prokaryotes

provide selective target

mainly bactericidal

43
Q

antibacterials - site of action - CELL MEMBRANE

A

high similarity to eukaryote cell membrane

few targets selective for bacteria

fewer drugs target the cell membrane

mainly bactericidal

44
Q

antibacterials - site of action - PROTEIN SYNTHESIS

A

many drugs

exploit differences between prokaryotic and eukaryotic ribosomes

selective target

45
Q

antibacterials - site of action - NUCLEIC ACID SYNTHESIS

A

many drugs

different cellular machinery

selective target

bacteria lack nucleus

mainly bactericidal

Infection and Immunity (17 decks)

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