Antibiotics That Inhibit DNA Gyrase And DNA Strand Breakers

Question 1

What is DNA gyrase and what is it’s function?

Answer 1

A topoisomerase that introduces left-handed superhelical turns into the DNA of bacteria using ATP. It is a crucial enzyme that maintains the negative superhelical tension of the bacterial chromosome

Question 2

Why is DNA gyrase an excellent antibacterial target?

Answer 2

Because mammals do not supercoil DNA and supercoiling of DNA is a complex process making it easy to disrupt

Question 3

What is the mechanism of action of quinolones?

Answer 3

They act by blocking the A subunit of DNA gyrase and prevent supercoiling of bacterial DNA

Question 4

Give 3 examples of second generation quinolones (flouroquinolones)

Answer 4

Ciprofloxacin, nofloxacin, ofloxacin

Question 5

Why do antibacterial DNA strand breakers such as nitrofurans require an anaerobic environment?

Answer 5

In order to form radical anions that extract a H from DNA causing cleavage of the sugar-phosphate backbone

Question 6

Give an example of a nitrofuran

Answer 6

Nitrofurantoin

Question 7

Which antibiotic do patients experience alcohol intolerance when taking?

Answer 7

Metronidazole

Question 8

Why do patients acquire c.difficile?

Answer 8

If a patient is treated with a broad spectrum antibiotic this eliminates much of the normal microflora and promotes intestinal overgrowth of c.diff

Question 9

What are the symptoms of a c.diff infection?

Answer 9

Diarrhoea, abdominal pain, fever and nausea

Question 10

How is c.diff treated?

Answer 10

Discontinue the inducing antibiotic to allow reconstitution of intestinal microflora. Give oral metronidazole (400mg every 8 hours for 7-10 days)