Antibiotic Activity at Bacterial Ribosome Sites

Antibiotic Inhibition of Protein Synthesis tRNA, mRNA and Ribosomes

Oct 12, 2009

Antibiotic Activity, Susceptibility Tests, NOAA U.S.

The mechanisms of inhibition of bacterial protein synthesis become clearer each year. The recent Nobel Prize in Chemistry rewarded the clearer understanding of ribosomes.

The premiere effects of antibiotics are the inhibition and killing of bacteria and other microbes that could harm or kill a human or animal. Unfortunately, the very organisms treated with antibiotics may become resistant to the antibiotics. Find out why antibiotics work, and sometimes do not work, against bacteria.

Types of Antibiotics and Their Antibacterial Activities

Typically, antibiotics are active against bacteria in one or more of five major ways:

membranes - distort and damage cause leakages of critical cell components, usually followed by death. Examples: polymyxin B, colistin.
walls - inhibit synthesis of the cell wall of glycopeptide or peptidoglycan. Examples: penicillin, cephalosporins, bacitracin, monobactams, carbapenems.
ribosomes - block, inhibit mRNA, tRNA or alter ribosomes or RNAs at ribosome. Examples: streptomycin, gentamycin, chloramphenicol.
nucleic acids - interfere with the structure, synthesis or functions of either RNA or DNA, or both. Examples: rifampin, naldixic acid, quinolones.
competitive inhibition - e.g. sulfa drugs involved with PABA and folic acid synthesis. Examples: sulfonamides, sulfadiazine.

Antibiotics That Affect Protein Synthesis and How It Happens

Listed following are some common antibacterial antibiotics that interfere with protein synthesis in one or more ways. There are unique differences in the structure and function of these different antibiotics as will be seen here.

Aminoglycosides – (streptomycin, gentamycin, kanamycin, amikacin, neomycin, netilmycin, tobramycin) — Inhibit initiation of protein synthesis and cause misreading of mRNA in prokaryotes and disrupt polysomes to form monosomes.
Macrolides – (tetracycline, minicycline, doxycycline) – Binds to the 30S subunit, block the site for binding of aminoacyl-tRNAs to the prokaryotic ribosome. Polypeptide chain cannot grow.
Chloramphenicol — (a natural nitrobenzene ring antibiotic that may cause aplastic anemia in patients) Inhibits the peptidyl transferase activity of the 50S ribosomal subunit of prokaryotes.
Erythromycin (clarithromycin, azithromycin, etc.) – Binds to the 50S subunit and inhibits translocation in prokaryotes.
Puromycin – Causes premature chain termination by acting as an analog of aminoacyl-tRNA in both prokaryotes and eukaryotes.

Protein synthesis is an integrated, precise series of steps and activities. Protein manufacture requires mRNA, tRNA, and the rRNA in the ribosomes with ribosomal-associated proteins. Disruption of this integrated system makes protein synthesis impossible, or so dysfunctional, that the cells become immobilized in growth (stasis), or are so severely damaged that they die. Either way, phagocytosis by macrophages (monocytes) and neutrophils internalizes bacteria and other microbes, and results in the destruction of the bacteria within by basic host mechanisms.

Microbial Resistance to Antibacterial, Anti-Protein-Synthesis Antibiotics, Mutation and Selection

Bacteria have very rapid division rates. Escherichia coli may divide as often as every 12-15 minutes under optimal conditions. Further, bacteria mutate to resistance at a rate of 1 in a million, to 1 in 10 million. Therefore, it is possible that some resistant mutants may have formed – even in the absence of any antibiotic. When the antibiotic is present these antibiotic-resistant mutants continue to grow, multiply and prosper.

What mechanisms do bacteria employ to become resistant to antibiotics that inhibit protein synthesis? Here is a brief list:

Membrane changes block entrance and penetration of the antibiotic into the cell's cytoplasm.
Enzymes degrade the antibiotic, or inactivate it by reactions of: phosphorylation, adenylation, or acetylation.
Ribosomes with altered, mutated, chemical structures prevent antibiotic attachment to those types of ribosomes.
Molecular pumps energetically transfer the antibiotic out of the cell.

Antibiotics are amazing and complicated, and represent the constant, major battle to kill microbial pathogens. Bacteria, with their specialized molecular mechanisms, may inactivate some antibiotics and outflank some of science's and medicine's best attempts to totally control these agents of disease.

Sources

Brooks, G.F., J.S. Butel and S. A. Moore. 2004. Medical Microbiology. 23rd ed., Lange Medical Books, McGraw-Hill, New York. 818pp

The copyright of the article Antibiotic Activity at Bacterial Ribosome Sites in Scientific Inquiry is owned by Donald Reinhardt. Permission to republish Antibiotic Activity at Bacterial Ribosome Sites in print or online must be granted by the author in writing.