Protein synthesis inhibitor antibiotics portray its anti-infective properties on the bacteria by disrupting the processes involved in generating new proteins in the bacterial cell thus stopping or slowing down bacterial proliferation. Its action is mainly on the ribosome level of the bacterial cell (Boundless, 2015). Protein synthesis inhibitors are selectively toxic since they will most likely act on the specific subunits of the ribosomes such as the 30s and the 50s subunit. The difference between prokaryotic and eukoryotic cells in terms of their ribosomal subunits is that bacterial ribosomes contain the 30s and 50s subunits while the ribosomes of mammalian cells have the 60s and a 40s subunits. Protein synthesis inhibitors do not affect the mammalian cells and that explains the drug being highly selective to the 30s and 50s subunits (Neal 2005).
There are various protein synthesis inhibitor drugs available at present. They work on the different stages in the mRNA translation proces of the proteins such as the initiation stage, elongation stage which includes the aminoacyl tRNA entry, ribosomal translocation, peptidyl transfer and proofreading. In addition, some of these drugs also work on the termination stage (Boundless, 2015). Examples of protein synthesis inhibitors are tetracyclines in which its action is on blocking the tRNA binding by blocking the A site of the ribosome (Neal, 2005). Another example is the aminoglycoside such as gentamicin and they work by causing an incorrect reading of the mRNA, thus an increased rate in the error of the protein synthesis by interfering the proofreading process. The streptogrammins on the other hand inhibit protein synthesis by causing a premature release on the bacteria’s peptide chain and the chloramphenicol type works by blocking the peptidyl transfer step of elongation on the ribosomal subunit 50s (Rang et al 2003).
Long, S. (n.d.) Aminoglycosides.
http://faculty.swosu.edu/scott.long/phcl/abagabs.htm
There is another kind of protein synthesis inhibitor which gained FDA approval in 2000 called Linezolid. This drug blocks the initiation complex formation by binding on the 50s subunit of the ribosome. According to Ford (2001), its advantage is revealed in one of the human studies related to its use in which the drug was found out to be 100 percent bioavalable through the oral route. As compared to other antibiotics that are given intravenously, its advantage is significant by reducing longer hospital stays with patients being able to take the antibiotic therapy at home. Furthermore, Linezolid is also able to treat some of the resistant bacteria such as the methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VRE) because its mechanism of inhibiting the protein synthesis occurs at the earliest stage which as is the initiation stage as compared to other drugs which are noted to have its action on the later stages (Klajn 2005).
A number of protein synthesis inhibitors can be taken orally which is an advantage when it comes to reducing patient’s hospital stays as well as hospital costs. In addition, because of a variety of them perform specific functions on inhibiting the protein synthesis of the bacteria at a specific stage, this group of antibiotics are capable of fighting off infections against a number of bacteria which includes the several gram-positive and gram negative bacteria. This is because of its action on the ribosomes as compared to other groups of antibiotics in which their action focus on the cell wall (Neal 2005). In addition, some of the drugs such as Tetracyclines can be used to control non-bacterial microbial infections or parasites such as malaria and elephantiasis (Steane n.d.).
In terms of the disadvantages of protein synthesis inhibitors, according to Neal (2005), there had been an increasing resistance against aminoglycosides (e.g. Gentamycin) against bacteria. In addition, Braunwald et al (2001) also mentions that some resistance related to this may be due to decreased antibiotic uptake which may also be due to alterations in the outer membrane of the bacteria. Also mentioned by Neal (2005) are the unwanted side effects and adverse effects in the use of protein synthesis inhibitors such as nephrotoxicity and ototoxicty for aminoglycosides, jaundice for macrolides, pseudomembranous colitis in clindamycin and bone marrow depression in chloramphenicol which is life threatening.
A lot of the common antibiotics are protein synthesis inhibitors. What's interesting about how this is classified is that just by the word itself, it already gives light as to what its action to the bacteria at the molecular level.
References:
Boundless (2015). “Inhibiting Protein Synthesis.” Boundless Microbiology. Boundless (online). Available at: https://www.boundless.com/microbiology/textbooks/boundless-microbiology-textbook/antimicrobial-drugs-13/functions-of-antimicrobial-drugs-154/inhibiting-protein-synthesis-779-7346/
Braunwald, E., Fauci, A., Kasper, D., Hauser, S., Longo, D. And Jameson, J.L. (2001). Harrison’s Principles of Internal Medicine. 15th Edition. New York. McGraw-Hill. pp.225-226
Ford, C. (2001). First of a Kind. (online). Available at: https://learn2.open.ac.uk/pluginfile.php/1382158/mod_resource/content/2/Ford_2001.pdf
Klajn, R. (2005). Linezolid. Molecule of theMonth. University of Bristol. School of Chemistry. (online). Available at: http://www.chm.bris.ac.uk/motm/linezolid/linezolid.htm (Accessed: June 8, 2015)
Rang, H.P., Dale, M.M., Ritter, J.M., and Moore, P.K. (2003). Pharmacology. Fifth Edition. Philadelphia. Elsvier Science Limited.
Walsh, C. (2000). Molecular mechanisms that confer antibacterial drug resistance. Nature. vol. 406. (online). Available at: https://learn2.open.ac.uk/pluginfile.php/1382167/mod_resource/content/1/Walsh.pdf ( Accessed: June 9, 2015).
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