Antimicrobial mechanism Flashcards

1
Q

Which microbes are beneficial

A

Microbiome, 95% of bacteria are in the GI tract

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2
Q

What features are on the outside of a bacteria cell

A

Cell wall (peptidoglycan) cell membrane

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3
Q

What features are on the inside of a bacteria cell

A
  • circular DNA
  • ribosomes (70s not 80s)
  • unique aspects of metabolic pathways
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4
Q

How does bacterial DNA fit inside the cell

A

Supercoiling

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5
Q

Negative supercoiling is usually in which direction

A

Left-handed

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6
Q

Features of negative supercoiling

A

Compact and loosen the two strands of DNA

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7
Q

Thermophilic bacteria have what kind of supercoiling

A

Positive supercoiling

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8
Q

Why do thermophilic bacteria have positive supercoiling?

A

protects DNA from denaturation in extreme conditions

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9
Q

What enzyme is responsible for supercoiling in gram-negative bacteria?

A

DNA Gyrase

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10
Q

What enzyme is responsible for supercoiling in gram-positive bacteria?

A

Topoisomerase IV

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11
Q

How does DNA gyrase and topoisomerase IV achieve supercoiling?

A
  • cutting one region of DNA double-helix
  • threading a second DNA region through the break
  • resealing the break
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12
Q

Name a first-generation quinolone

A

Nalidixic acid

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13
Q

What was Nalidixic acid used to treat?

A

Active against mainly gram -ve bacteria, treatment for UTIs, bacteriocidal

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14
Q

Second generation quinolones are also known as

A

Fluoroquinolones

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15
Q

What did fluoroquinolones have an increased activity on

A

Gram +ve bacteria

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16
Q

Name two examples of fluoroquinolones

A

norfloxacin
ciprofloxacin

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17
Q

Name an example of a third-generation quinolone

A

Levofloxacin

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18
Q

What benefit did third generation quinolones have over previous generations?

A

Active against streptococci
sufficiently broad spectrum to be used before bacteria identified
indicated in pneumonia and urinary tract infections

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19
Q

What environment do nitroimidazoles require?

A

Anaerobic environment

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20
Q

What is the nitro group in nitroimidazoles reduced by?

A

Bacterial electron-transport system

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21
Q

Name the two radicals formed in nitroimadazoles?

A

nitro radical anion
imidazole radical

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22
Q

What does the imidazole radical extract from DNA

A

A H atom

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23
Q

Name a nitroimidazole

A

Metronidazole

24
Q

What is the mechanism of action of metronidazole?

A

nitro radical anion formed and then imidazole radical which extracts a H from DNA, breaking the strand apart.

25
What are nitroimidazoles used to treat?
anaerobic bacterial and protozoal infections e.g. bacterial vaginosis, acute oral infections, and C.difficile
26
What are the side effects of nitroimidazoles?
alcohol intolerance, swollen, red or hairy tongue
27
What organelle makes proteins?
Ribosome
28
What is there a higher chance of in bacteriostatic antibiotics?
antibiotic resistance
29
Oxazolidinones block....
50s/30s binding
30
Chloramphenicol/ macrolides block...
peptide chain transfer inhibits protein synthesis, bacteriostatic
31
How do tetracyclines inhibit protein synthesis?
interfere with tRNA binding which means that the corresponding amino acids cannot join together so protein synthesis is disrupted and inhibits bacteria cell growth.
32
Oxazolidinones
binds to 50s subunit active against multiple-resistance bacteria including MRSA used against gram +ve hospital-acquired infections e.g. Staphylococcus aureus, S. epidermis and steptococcus pneumonia, where other treatments are unsuccessful
33
Tetracyclines
interfere with tRNA binding binds to 30s and stops aminoacyl tRNA from binding very widely used antibiotic, with broad spectrum
34
What are tetracyclines used to treat?
Lyme disease, malaria and acne
35
Macrolides
binds to 50s subunit blocks peptide chain transfere active against most gram +ve bacteria e.g. ear infections, streptococcal pharyngitis (bacterial tonsillitis) used as a first-line treatment for penicillin-allergic patients
36
Erythromycin
binds near peptidyl transferase centre blocks exit tunnel for the growing peptide inhibits peptide bond formation and translocation
37
Chloramphenicol belongs to which class
amphenicols
38
Chloramphenicol works by
binds to 50s subunit and also prevents peptidyl transferase reaction
39
What two antibiotics cannot be used in combination
Chloramphenicol and macrolides as they occupy the same region
40
Synthesis of DNA uses which molecule
Folate
41
What does DHFR (dihydrofolate reductase) do?
Dihydrofolate reductase (DHFR) catalyzes the reduction of dihydrofolate to tetrahydrofolate (THF). THF is needed for the action of folate-dependent enzymes and is thus essential for DNA synthesis and methylation.
42
Metabolic pathway of folate
folate > DHFR > dihydrofolate > DHFR > tetrahydrofolate
43
DNA synthesis inhibitors are sometimes known as
Antimetabolites
44
Name two DHFR inhibitors
Trimethoprim Methotrexate
45
Trimethoprim mimics which ring of folate
pteridine ring
46
Trimethoprim is used in combination with other antibiotics to treat which condition?
UTI
47
Methotrexate mimics which ring
Pteridine ring of folate (closer mimic than trimethoprim)
48
What does methotrexate target?
human DHFR so mainly used against cancer and rheumatoid arthritis
49
Sulfa Drugs
inhibits DHPS by mimicking PABA substrate of DHPS
50
Sulfamethoxazole
used with trimethoprim in co-trimoxazole
51
What is sulfamethoxazole used to treat
UTIs and pneumocystis carinii pneumonia in AIDs patients.
52
Which enzyme catalyses dihydrofolate in bacterial cells?
dihydropteroate synthase
53
How do sulfa drugs work?
Inhibit DHPS mimicking PABA substrate of DHPS
54
Why is sulfamethoxazole used in combination with trimethorpim
Folic acid is made from PABA through a step-by-step process involving two enzymes. The sulfa drug inhibits the first enzyme and trimethoprim inhibits the second enzyme. This double inhibition is called the sequential blockade and produces the death of a bacterial cell.
55
What can resistance bacteria increase the production of to compete with sulfa drug
PABA
56
Explain the process of sequential blocking
action of two or more inhibitors each of which acts on the same metabolic pathway but upon different enzymes.