18.01.5 Inhibitors of Bacterial Protein Synthesis

Within the cell, ribosomes are the sites of protein synthesis. The ribosomes and protein synthesis in bacteria and humans are different. In particular, the structure of the bacterial ribosome is different from that of the mammalian ribosome. Thus, it is possible to inhibit bacterial protein synthesis without altering the protein synthesis of the human, and this gives selective toxicity against the microbes over the humans. In the process of bacterial protein synthesis, the first step involves the transfer (t) RNA with an attached amino acid binding to the ribosome (Figure 18.2).

Figure 18.2 Steps involved in bacterial protein synthesis (Copyright Sheila Doggrell, QUT)

The second step in bacterial protein synthesis is that the tRNA with the amino acid attached forms base pairs with the ribosome. The third step is transpeptidation, when the amino acid chain is transferred onto incoming tRNA-amino acid, with the addition of the protein to the amino acid, so the protein has one more amino acid on it. The fourth step is translocation, when the ribosome moves along the mRNA and releases the free tRNA allowing next tRNA-amino acid to bind. Finally, there is separation of the protein from the ribosome.

Every step in this bacterial protein synthesis at the ribosome is a step we can interfere with using drugs. For instance, the binding of amino acid carrying tRNA- to the ribosome is inhibited by the group of antibiotics known as the tetracyclines. The second step, the formation of base pairs, is inhibited by the aminoglycosides. The third step, the transpeptidation, is inhibited by chloramphenicol, and the fourth step, the translocation of the ribosome alone the mRNA, is inhibited by the macrolides. Each of these antibiotics is discussed below.