Tetracycline Resistance on Protein Synthesis

Abstract

Tetracycline is an antibiotic with powerful antibacterial activities against a wide variety if microorganisms. It is a potent antibacterial antibiotic that inhibits protein synthesis to work and it is also a good medication because of its low toxicity and adverse reaction, oral absorption, and effectiveness against disease-causing germs. Its major mechanism of action is based on inhibition of protein synthesis. The relatively low toxicity & allergic reaction, effective oral absorption, and wide range of effectiveness against disease causing microorganisms are reasons why tetracycline is regarded as a good medication. Tetracycline mechanism of action is mainly its inhibitory ability of protein synthesis. It inhibits aminoacyl-tRNA from binding to the ribosome's A site and thus prevent any further amino acid addition to the developing polypeptide chain. It inhibits protein synthesis at once and disrupt several enzymatic activities essential to propagation and survival. This inhibitory ability is less apparent in surrounding human/animal cells during treatment, which is due to inability of such cell to pump tetracycline into their cytoplasm against concentration gradient unlike bacteria cells. In addition, its ability to disrupt cellular membrane causes organelles o leak from the cell and thus impedes propagation or multiplication. However, tetracycline resistance was observed over time. Tetracycline resistance has been observed to be caused by the action of intrinsic enzymes synthesized to inactivates or degrade it. Also, the excretion and efflux of tetracycline from the cytoplasm, thus reducing cytoplasmic concentration and ultimately, its efficacy. Such microorganism possesses membrane proteins or transporters that can export tetracycline at a rate equal to or greater than its influx rate. The transporters could be tetracycline specific or a multidrug transporter. Another mechanism of tetracycline resistance is known as ribosome's protection. Although the mechanism is not well known, ribosome protective resistance protein (TetM) binds to the ribosome's binding site. This molecule has similarities to elongation factor, and it allows the elongation of polypeptide chain while reducing the affinity of the binding site to tetracycline. This ultimately makes tetracycline ineffective against the microorganisms. This mechanism can also be used in conjunction with efflux mechanism of tetracycline resistance.