Biotechnology - Yu.O. Sazykin 2006

Special Biotechnology
Problems of Discovery, Development, and Application of Antibiotics in Medical Practice
Mechanisms of Action of Antibiotics - Bacterial Protein Synthesis Inhibitors

These include all Aminoglycosides (streptomycin, gentamicin, etc.), as well as Tetracyclines, erythromycin, chloramphenicol, and certain Other Antibiotics. These antibiotics interact with bacterial Ribosomes, thereby halting Protein Synthesis within the ribosomal systems. The cytoplasmic ribosomes of animal Cells react to these agents much more weakly or fail to bind them altogether. The mitochondrial ribosomes of animal cells (which share properties similar to bacterial ones) are shielded from the aforementioned antibiotics by the mitochondrial membrane. These two factors make it clinically feasible to use such antibiotics, meaning they have low toxicity for humans. Conversely, there are antibiotics that interact with the ribosomes of both microorganisms and animal cells; these are not used in medical practice, but are instead produced as Reagents for biochemical and molecular biological research (for instance, the antibiotic cycloheximide).

As a rule, Protein Synthesis Inhibitors are bacteriostatic substances. The cessation of protein synthesis does not inherently lead to Cell death. In in vitro experiments, cells cease division and gradually, very slowly, die off. However, if an antibiotic induces bacteriostasis within a living Organism, the non-dividing cells decline in number much more rapidly because they are eliminated by the host organism's immune defenses.

Among the protein synthesis inhibitors are also bactericidal substances—namely, the large group of aminoglycoside antibiotics. These antibiotics interact with the small ribosomal subunit, binding specifically to the site where mRNA codons are recognized by tRNA anticodons. As a result, recognition accuracy is compromised. The Proteins synthesized by the ribosomal (or rather, polysomal) system during this process incorporate Amino Acids that do not match the Amino Acid Sequence encoded in the mRNA. This phenomenon is known as the "disruption of Genetic Code transmission accuracy at the Translation stage."

Although aminoglycosides rapidly halt protein synthesis, the specific nature of their binding site on the ribosome allows a certain number of aberrant protein molecules with incorrect Amino acid sequences to be released from the ribosomal systems before they cease functioning. These proteins, referred to as "lethal proteins," become integrated into the bacterial cell's cytoplasmic membrane, disrupting its molecular Organization. The Cell begins to lose low-molecular-weight metabolites, Coenzymes, and inorganic ions. Ultimately, all of this leads to a disruption in enzymatic reactions and results in cell death.