Antibiotics

The term “antibiotics” emerged in 1942, referring to substances that inhibit the growth and reproduction of microorganisms. Microorganisms, molds, or fungi produce antibiotics, which target essential molecular cell mechanisms. These mechanisms are vital not only for microorganisms but sometimes also for the recipient’s functions. Many antibiotics exhibit anti-cancer properties because they target rapidly dividing cells, such as bacteria, cancer cells, and blood cell precursors. Researchers often use antibiotics to study biochemical processes because they inhibit specific molecular mechanisms.

Puromycin stands out as a well-studied antibiotic that inhibits bacterial protein biosynthesis. Streptomyces alboniger produces puromycin, which mimics the 3′ end of the aminoacyl-tRNA acceptor stem, allowing it to bind to the A site of the ribosome (50S large subunit) and form a peptide bond—peptidylpuromycin. However, without a carboxyl group, puromycin stops the elongation of the polypeptide chain, leading to premature termination of protein synthesis.

Actinomycin D inhibits protein synthesis and possesses anti-tumor effects. However, due to high toxicity, it sees limited use. It inhibits all cellular RNA synthesis types, especially mRNA, by hindering DNA-dependent RNA polymerase. By binding to the DNA chain with deoxyguanosine, actinomycin D halts its template functions, thereby inhibiting DNA transcription.

Rifamycin inhibits cellular RNA synthesis by binding to DNA-dependent RNA polymerase, with bacterial RNA polymerase being particularly sensitive to it. Rifamycin treats tuberculosis and affects animal organisms minimally. Its mechanism of action differs from that of actinomycin D. Rifamycin also boasts antiviral properties and treats trachoma caused by DNA-containing viruses.

Tetracycline inhibits protein biosynthesis in bacteria by binding to the 30S ribosomal subunit, preventing aminoacyl-tRNA from binding to the 30S ribosome’s aminoacyl center by easily crossing the cell membrane.

Chloramphenicol (levomycetin) attaches to the 50S ribosomal subunit, inhibiting protein synthesis in bacteria, mitochondria, and chloroplasts by blocking peptidyl transferase and peptide bond formation, while not affecting eukaryotic protein synthesis. Conversely, cycloheximide inhibits eukaryotic 80S ribosome peptidyl transferase and, by binding to the large ribosomal subunit, halts translocation. It does not affect bacterial, mitochondrial, and chloroplast 70S ribosomes.

Lincosamides, such as lincomycin and clindamycin, act similarly to erythromycin, which inhibits ribosomal translocation by binding to the 50S subunit. Erythromycin affects both Gram-negative and Gram-positive bacteria. Streptomycin and gentamicin cause errors in translocation and disrupt the normal reading of the genetic code, leading to decreased specificity of mRNA triplets. These antibiotics inhibit the initiation of protein synthesis, primarily targeting Gram-negative bacteria. Neomycin and kanamycin exhibit similar effects.

Penicillins are not true protein synthesis inhibitors; their antibacterial effect involves inhibiting hexapeptide synthesis in bacterial cell walls, a different mechanism from ribosomal synthesis. Erythromycin and oleandomycin inhibit the activity of carriers (translocases) during information transfer (translation), similar to cycloheximide, but exclusively in 80S ribosomes, thereby inhibiting protein synthesis in animal cells.

Source | Glossary of Most Commonly Used Biomedical Terms and Concepts | Lithuanian University of Health Sciences | Academician Professor Antanas Praškevičius, Professor Laima Ivanovienė