(47)
17. Beskrive hvad antibiotiske inhibitorer af translationen er, og hvordan
antibiotisk resistens kan opstå
Devlin, s.254-5
Devlin, s.347
Stryer, s. 838-4
Protein synthesis is central to the continuing of life and reproduction of cells. An organism can gain a biological advantage by interfering with the ability of its competitors to synthesize proteins, and many antibiotics and toxins function this way.
Many antibiotics work by inhibiting proteins synthesis. They exploit the difference between prokaryotic and eukaryotic ribosomes.
Several examples:
Streptomycin – binds to the 30S subunit of prokaryotic ribosomes, interferes with the initiation process and causes misreading of mRNA (initiation)
Tetracycline – Binds to the 30S subunit and inhibits binding of aminoacyl tRNA. (initiation)
Puromycin - resembles an aminoacyl t-RNA and binds to the A site, acting as an acceptor in the peptidyltransferase reaction. However, it can not serve as a donor, so it terminates the translation prematurely, leading to the release of an incomplete and non-functional protein. Has effect on both pro- and eukaryotes. Not too good for our cells. (elongation)
Chloramphenicol
– binds to
the peptidyltransferase center in the 50S subunit and inhibits forming of a
peptide bond. (elongation)
Antibiotic resistance can occur with the help of transposons – small DNA sequences that have the ability to jump between chromosomes. Transposon sequences contain genes that facilitate their “jumping”, and often contain antibiotic resistance sequences, toxin production sequences etc.
The antibiotic resistance sequence can code for a protein that hydrolyses the antibiotic.
Plasmids, independent DNA molecules in bacteria, contain genes that facilitate their transfer from one bacterium to another. Plasmids can contain transposons.
As the plasmids transfer, e.g. between different infecting bacterial strains, the transposons containing antibiotic resistance genes are moved into the new bacterial strain. Once inside a new bacterium, the transposon can duplicate onto the chromosome and become permanently established in the cell’s lineage. The result is that more and more pathogenic bacterial strains have become resistant to increasing number of antibiotics.
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