Chromosomal Double Helix DNA

Bacteria as procariotic microorganisms have no nucleus; their DNA is just a chromosome spread in the bacterial cell.

In E. coli the length of a DNA strand is around 1,300 µm. On the other hand, the cell which it has to fit into is only 2 µm long.

Gyrase

To make it fit, it has to be supercoiled. Gyrase molecules are responsible for correct coiling by cleaving and resealing the DNA double helix.


Intact Bacterial Cell

Supercoiled material is introduced into the linear DNA double helix, which results in the highly condensed three-dimensional structure of the DNA usually present inside the cell.

With Baytril® – Exploding Bacterial cell

Baytril® interferes with bacterial DNA metabolism by the inhibition two enzymes: topoisomerase II (also called DNA gyrase) and topoisomerase IV. In gram-negative organisms DNA gyrase is the primary target, whereas in gram-positive bacteria topoisomerase IV is found to be most affected. The function of DNA gyrase is to introduce supercoils into the linear DNA double helix, which result in the highly condensed three-dimensional structure of the DNA usually present inside the cell. The function of topoisomerase IV still is barely understood.

Depending on the type of bacteria, these enzymes represent either the primary or secondary target of antimicrobial action. In gram-negative bacteria, such as E.coli, Baytril® predominantly inhibits DNA gyrase, whereas for gram-positive organisms like staph. aureus, topoisomerase IV is the principle target.

Models to explain the activity of Baytril® at the target site only exist for DNA gyrase: During the supercoiling process, both DNA strands are cleaved by DNA gyrase at four base pair staggered sites, forming a "quinolone binding pocket". Two fluoroquinolone molecules self-assemble inside the pocket in a dimer structure and attach to the gyrase-DNA complex electrostatically, which stabilizes the intermediate stage of this reaction step. Permanent gaps in the DNA strands induce synthesis of repair enzymes (exonucleases), initiating uncoordinated repair processes, which result in irreversible damage to the DNA and, finally, cell death.

View Video: Baytril® Effect in bacteria

video-respresenter

The video was taken at Bayer Laboratories, Wuppertal, Germany.
Microscopical resolution was 1000 x.

See the video: Baytril® Effect in Bacteria