Question

What are the antibiotic resistant genes for doxycycline? If possible, give the gene sequence.

Answer 1

Doxycycline:

A synthetic TETRACYCLINE derivative with similar antimicrobial activity. Animal studies suggest that it may cause less tooth staining than other tetracyclines. It is used in some areas for the treatment of chloroquine-resistant falciparum malaria ( MALARIA, FALCIPARUM).

Synonyms: Doxycycline   DOXY   Doxychel

Doxycycline are a group of broad-spectrum antibiotics whose general usefulness has been reduced with the onset of antibiotic resistance. Despite this, they remain the treatment of choice for some specific indications.

Tetracycline or Doxycycline inhibits cell growth by inhibiting translation. It binds to the 16S part of the 30S ribosomal subunit and prevents the amino-acyl tRNA from binding to the A site of the ribosome. The binding is reversible in nature.

Cells become resistant to tetracycline by at least three mechanisms: enzymatic inactivation of tetracycline, efflux, and ribosomal protection. Inactivation is the rarest type of resistance, where an acetyl group is added to the molecule, causing inactivation of the drug. In efflux, a resistance gene encodes a membrane protein that actively pumps tetracycline out of the cell. This is the mechanism of action of the tetracycline resistance gene on the artificial plasmid pBR322. In ribosomal protection, a resistance gene encodes a protein that can have several effects, depending on what gene is transferred. Six classes of ribosomal protection genes/proteins have been found, all with high sequence homology, suggesting a common evolutionary ancestor.

Possible mechanisms of action of these protective proteins include:

1. blocking tetracyclines from binding to the ribosome
2. binding to the ribosome and distorting the structure to still allow t-RNA binding while tetracycline is bound
3. binding to the ribosome and dislodging tetracycline.

All of these changes to ribosomes are reversible (non-covalent) because ribosomes isolated from both tetracycline-resistant and susceptible organisms bind tetracycline equally well in vitro.