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INFECTION AND IMMUNOLOGY > J Letchford Lec 1 Modes of action > Flashcards

J Letchford Lec 1 Modes of action Flashcards

1
Q

Antimicrobials are chemicals which kill or ____ microbial growth.

A

Inhibit

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2
Q

Bacteriostatic =

Bactericidal =

A

Inhibit

Kill

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3
Q

Most antimicrobials only kill actively _____ bacteria so also rely on host immune system to eradicate all bacteria.

A

Growing

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4
Q

What are the 4 main sites of anti-microbial action?

A

1) Cell Wall
2) Cell membrane (x many targets as pro & eukaryote cell mem are similar)
3) Nucleic acid synthesis
4) Protein synthesis (side effects as pro & eukaryote ribosomes are similar)

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5
Q

What makes up the bacterial cell wall?

How are the neighbouring molecules in this held together?

A
  • Peptidoglycan (large macromolecule)
  • Glycosidic bonds hold residues together and 3rd AA and terminal AA of glycan chains cross-link by short peptide bridges.
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6
Q

The glycol chains act as a backbone to ______, and is composed of altering residues of N-___ ____ ____ (NAM) and N-____ _____ (NAG).

A

Peptidoglycan
N-Acetyl Muramic Acid
N-Acetly Glucosamine

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7
Q

In peptidoglycan cell walls, each molecule of NAM has a pentapeptide attached consisting of AAs. This glycan pentapeptide repeat unit is ____-_____ to adjacent ____ chains, through direct _____ linkage or ____ inter-bridge.

A

Cross-Linked
Glycan
Peptide
Peptide

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8
Q

For PG cross linking to occur, _______ are needed.

A

Transpeptidases

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9
Q

How do B-lactams exert their action?

A

1) They bind Penicillin Binding Proteins (PBPs)
- Transpeptidases (needed to cause cross linking)

This then prevents cross-linking between neighbour peptide side chains.

Cells then lose shape due to lack of proper cell wall and the cell dies.

2) Mimic d-ala-d-ala residues on peptide side chain to prevent cross linking
3) Stimulate autolysins - break down cell wall (indirect effect)

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10
Q
  • Gram negative bacteria have an ____ ______ that is not present in Gram positive bacteria.
  • Gram negative bacteria have thinner/thicker peptidoglycan layer than gram positive bacteria
  • B lactam drugs need to get through the outer membrane and peptidoglycan layer before binding to _____ ____ _____ on the cytoplasmic membrane and inhibiting cross linking.
A

Outer membrane

Thinner

Penicillin binding protein

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11
Q

Glycopeptides inhibit the synthesis of the ___ ___.

Two examples of glycopeptides are _____, ______.

These antimicrobials bind terminal _-__ - _-__ on peptide side chain, preventing _________ enzyme from adding PG monomer onto glycan chain.

It prevents cross linking

A

Cell wall

Vancomycin and Teicoplanin

d-ala - d-ala

Transglycosylase enzyme

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12
Q

Polymyxins are inhibitors that act at the ___ _______.
e.g Polymyxin B and E (Colistin)

These drugs work on gram _ve bacteria.

Why is this?

A

Cell membrane

Negative

Because Polymyxins act on the cell membrane and gram positive bacteria do not possess an outer membrane.

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13
Q

Polymyxins disrupt the cells outer _____ causing _____ of cytoplasmic contents.

A

Membrane

Leakage

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14
Q

Some antimicrobials act on ______ Acid (NA)

Metabolic inhibitors of NA synthesis
e.g S_______des & T______im

A

Nucleic Acid

Sulfonamides and Trimethoprim

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15
Q

Some antimicrobials affect ____ replication

e.g F_______ones

A

DNA

Fluoroquinolones

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16
Q

Some antimicrobials affect ___ polymerase

e.g ____mycins

A

RNA

Rifamycins

17
Q

Some antimicrobials affect DNA directly

e.g Nitro_____oles and Metra_____

A

Nitroimidazoles

Metranidazole

18
Q

Inhibitors of ____ replication include
C______acin (gram-) and L______acin (gram+&-)

These antimicrobials either Type 2 (DNA ____) AND/OR Type 4 ________.

A

DNA

Ciprofloxacin and Levofloxacin

Gyrase

Topoisomerase

19
Q

DNA Gyrase: removes DNA _____ ahead of replication fork

A

Supercoils

20
Q

Topoisomerase 4: separates out DNA after _____.

A

Replication

21
Q 
Inhibitors of Protein synthesis:
M\_\_\_\_\_des
Strep\_\_\_\_mins
Linc\_\_\_\_des
Oxaz\_\_\_\_\_\_ones
Amin\_\_\_\_\_\_
Tet\_\_\_\_\_\_
Chlor\_\_\_\_\_\_\_
Fusi\_\_ \_\_\_\_
A 
Macrolides
Streptogramins
Lincosamides
Oxazolidinones
Aminoglycosides
Tetracyclines
Chloramphenicol 
Fusidic acid
22
Q

__s ribosomes and __s ribosomes come together to make __s ribosomes

A

30s and 50s to make 70s

23
Q

Protein synthesis:

INITIATION:

1) fmet-tRNA brought to ___ start codon (_ site)
2) 30s subunit attaches to ____
3) __ subunit completes initiation complex

ELONGATION:
1) 2nd \_\_\_\_ enters A site
2) Peptide bond between 1st and 2nd \_\_.
3) Translocation and release of \_\_\_.
1st \_\_\_\_ comes off ribosome
2nd \_\_\_\_ enters P site
3rd \_\_\_\_ enters A site

TERMINATION (reach stop codon)

A

AUG (p site)
mRNA
50s

tRNA
AA
tRNA
tRNA
tRNA
tRNA
24
Q

Inhibitors of protein synthesis:

Aminoglycosides/Oxazolidinones (Cidal agents)
e.g G_____ / L_____

MOST AG’s bind __ subunit:
DECREASE initiation and assemble of _____
DECREASE binding of ____ in _ site and translocation

SOME AG’s and Oxazolidinones bind ___ subunit:
DECREASE assemble of _______ complex.

A

Gentamicin
Linezolid

30s
Ribosome
tRNA in A site (acceptor site)

50s
Initiation

25
Q

Inhibitors of protein synthesis:

Tetracyclines (Static agents)
e.g D_______, M______

Bind ___ subunit of ribosome
DECREASE binding of _____ in _ site

A

Doxycycline
Minocycline

30s
tRNA in A site (acceptor site)

26
Q

Inhibitors of protein synthesis:

Chloramphenicol

Binds to __ subunit
DECREASES peptide ____ formation

A

50s

Bond

27
Q

Inhibitors of protein synthesis:

Macrolides
e.g E______, C______

Binds __ subunit
DECREASES ______ and release of tRNA

(doesn’t affect peptide bond formation but the ribosome can’t move along the strand! - this means incomplete polypeptides are released)

A

Erythromycin
Clarithromycin

50s
Translocation (ribosome moving along mRNA)
28
Q

Inhibitors of protein synthesis

Fusidic acid

Binds to EF-_ ribosome complex
DECREASES translocation of tRNA from _ to _ site

A

EF-G (elongation factor that supplies energy for translocation)

A site to P site

29
Q

Other antimicrobials:

Affecting cell wall synthesis:
Cycloserine, Bacitracin

Acting on cell membrane
Dapto___ (Cubicin)

Affecting protein synthesis
Lincos___, Streptogramins

Affecting nucleic acid
Sulfon____/ Tri_____, Rifa____

A

Daptomycin

Lincosamides

Sulfonamides, Trimethoprim, Rifamycins

INFECTION AND IMMUNOLOGY (14 decks)

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