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PCL470 > Lecture 13: Antibacterials > Flashcards

Lecture 13: Antibacterials Flashcards

1
Q

Salvarsan

A

identified by Ehrich to treat syphillis

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2
Q

3 classifications for bacteria

A
  1. shape
  2. aerobic or anaerobic
  3. gram staining
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3
Q

Gram positive bacteria

A

thick peptidoglycan layer in cell wall but no outer membrane
stain purple with crystal violet dye

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4
Q

Gram negative bacteria

A

extra outer membrane
also have peptidoglycan wall but less thick
tougher to treat

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5
Q

Disc diffusion method

A

test sensitivity of bacteria to drug

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6
Q

Bactericidal vs Bacteriostatic

A

bactericidal: kill bacteria (irreversible)
bacteriostatic: blocks reproduction of bacteria (reversible after agent removed)

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7
Q

Penicillin

A

bactericidal
lactam ring binds and inhibit DD transpeptidase
prevent crosslink and formation of new cell wall
orally bioavailable

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8
Q

2 resistance mechanism against penicillin

A
  1. evolved thicker outer membrane
  2. acquire penicillinase gene (inactivate penicillin)
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9
Q

Vancomycin

A

bactericidal
inhibit cell wall synthesis by directly binding to D-Ala-D-Ala peptides
prevent incorporation into a growing peptide chain
blocks elongation and crosslinking

deliver intravenously

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10
Q

Resistance mechanism to vancomycin

A

bacteria change precursor D-Ala-D-Ala to D-Ala-D-Lac

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11
Q

Polymyxins

A

bactericidal
directly binds to LPS in outer cell membrane
cause holes
leakage

delivered orally

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12
Q

Tetracyclines

A

broad spectrum antibiotic
directly binds to 30S subunit of bacterial ribosome
block binding of tRNA
inhibit bacterial protein synthesis
bacteriostatic

orally bioavailable

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13
Q

Azithromycin

A

macrolide-based antibiotic
bind 23s rRNA of the 50s ribosomal subunit
blocks translocation during protein synthesis
bacteriostatic

orally bioavailable

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14
Q

Linezolid

A

binds to 23s rRNA of 50S subunit
prevent formation of 70S initiation complex
bacteriostatic

very bioavailable in oral and IV
broad spectrum

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15
Q

Ciprofloxacin

A

bactericidal
binds to DNA gyrase
block proper compaction and storage of DNA

good oral bioavailability
do not take with milk
Ca2+ can chelate the drug and prevent absorption

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16
Q

Metronidazole

A

Bactericidal
PRODRUG
activated by bacterial enzyme to generate a toxic radical
widespread DNA damage

high bioavailability
adverse reactions: radical gets out of bacterial cell and damage healthy cells

17
Q

Trimethoprim

A

bacteriostatic
binds to bacterial DHFR enzyme
inhibit folic acid synthesis
block DNA synthesis

TERATOGENIC, do not use in pregnancy

18
Q

5 steps in bacteriophage replication cycle

A
  1. attachment
  2. penetration
  3. replication
  4. maturation
  5. release (lysis ,explode)
19
Q

2 states of bacteriophage

A

lytic - actively reproducing, bursting and killing bacteria
lysogenic - not actively killing bacterial cells (prophage)

20
Q

Phage therapy

A

orally as pill with antacid to gut
0.1% transcytoses
very selective but hard to find correct strain match (use cocktails)

21
Q

4 ways of bacteriophage resistance from bacteria

A
  1. mutations of outer receptor so phage cannot attach
  2. SIE (superinfection exclusion) system - block entry of phage by inactivating critical enzymes
  3. methylation of bacterial DNA, DNA cleavage not allowed for phage DNA
  4. adaptive immunity from CRISPR
22
Q

Cas13

A

cuts RNA instead of DNA
have collateral damage (nuclease domain remains active after first cut)
bactericidal

23
Q

Anti-CRISPR proteins (ACRs)

A

used by bacteriophage

block crRNA loading
acetylates PAM sensing lysine residue

turn off CRISPR system

24
Q

4 Considerations of using Cas9 and Cas13

A
  1. can cause immune reaction towards cas9 and cas13
  2. off target DNA-RNA cleavage
  3. can cause antimicrobial resistance genes from repair mechanism
  4. hard to deliver through bacterial cell wall and membrane
25
Q

SNAPPS

A

insert into bacterial membrane and cause lysis
bactericidal
“star-shaped dendrimer with 16 peptide arms”
excellent activity against MDR

26
Q

2 mechanism of Silver nanoparticles (AgNPs)

A

1 (particles). structurally disrupt membrane through ADHESION, interact with ribosome and generate ROS
2 (silver ions). silver ions can interact with SULFHYDRYL proteins and DNA phosphate backbone

bactericidal
not orally bioavailable, use topically or injected

27
Q

Polymeric nanoparticles (Chitosan)

A

cationic polymers can interact with negative charge in membrane and EPS (extracellular polymeric substances)
effective vs biofilms

28
Q

Liposomal nanoparticles for drug delivery

A

enhance stability, solubility, biocompatibility, controlled drug release
use cationic lipid DOTMA

PCL470 (14 decks)

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