In this blog post, we will examine the process by which bacteria synthesize proteins based on genetic information stored in their DNA, as well as the mechanism by which antibiotics target this process to inhibit bacterial growth and survival.
Protein Synthesis in Bacteria
People constantly consume food to survive. To eat, food must be properly prepared, and to prepare it, a cookbook is needed. If the cookbook is in the library, you can copy or take a photo of the page containing the information for the dish you need, bring it home, and cook while referring to it. Similarly, living organisms are constantly active to survive, regulating their own states through processes such as metabolism and signal transduction. And at the center of these activities are proteins. Not only in humans but also in tiny microorganisms and bacteria, proteins are involved in various life processes—such as transport, metabolism, signal transduction, and replication—and have a profound impact on the survival of organisms. As in the cooking analogy mentioned earlier, proteins can be seen as the dish itself. Since proteins are so important, several steps are required to produce them, and this process can also be thought of as corresponding to the cooking process described earlier.
First, the “cookbook” for cooking is DNA. DNA contains not only the genetic information necessary for protein synthesis but also a wide range of genetic information for living organisms. Organisms must select and utilize the genetic information they need from the entire DNA sequence. Once the section of DNA containing the information for the required protein is selected, RNA polymerase unravels that portion of the DNA and transfers the genetic information from DNA to RNA through a process called transcription. This is similar to copying or taking a photograph of the necessary section of a cookbook. Of course, since this process involves creating a copy, there are differences between DNA and RNA, just as the paper of a cookbook differs from copy paper or a photograph. DNA is composed of deoxyribose, while RNA is composed of ribose; DNA uses the bases A, G, C, and T, whereas RNA uses the bases A, G, C, and U. The fact that RNA has a relatively less stable structure than DNA is related to its role in providing temporary access to genetic information when needed, rather than preserving it over the long term. In particular, since mRNA can be degraded after a certain period following its synthesis, it prevents the continuous overproduction of proteins and regulates protein synthesis. Therefore, when the information necessary for protein synthesis is no longer needed, the mRNA is degraded in the cytoplasm, and protein synthesis using that mRNA is halted.
Just as you must begin cooking after copying a recipe in order to eat the food, once the information from mRNA is transmitted to the ribosome, bacteria synthesize polypeptides—chains of amino acids that make up proteins—through a process called translation. Unlike eukaryotes, prokaryotes such as bacteria do not have a nuclear membrane separating genetic material from the cytoplasm; therefore, transcription and translation do not occur in separate compartments. Therefore, a ribosome can bind to the mRNA produced during transcription, allowing translation to begin. The cellular structure responsible for translation is the ribosome. Ribosomes are not membrane-bound organelles but are composed of rRNA and proteins, and are divided into a small subunit and a large subunit. In prokaryotic cells, the 30S ribosomal subunit and the 50S ribosomal subunit combine to form a 70S ribosome. Here, “S” stands for the Svedberg unit, a sedimentation coefficient that describes the rate at which a particle settles during centrifugation. Therefore, the S value is not determined solely by density or mass. For translation to begin in bacteria, the ribosome must recognize the exact translation start site on the mRNA. In typical bacterial mRNA, a Shine-Dalgarno sequence is present upstream of the start codon AUG; this sequence binds to a complementary sequence on the 16S rRNA, allowing the 30S subunit to position itself at the appropriate location on the mRNA. Subsequently, an initiation tRNA bound to the translation initiation factor and formylmethionine (fMet) joins to form the initiation complex; as the 50S large subunit binds, the 70S ribosome is completed, and translation begins in earnest. Subsequently, tRNA molecules matching the codon enter the ribosome along with amino acids, and the polypeptide chain is elongated as the amino acids are linked by peptide bonds. During this elongation process, when a termination codon—UGA, UAG, or UAA—is reached, a release factor acts to release the newly synthesized polypeptide, and the ribosomal complex disassembles, terminating translation. The polypeptide then undergoes folding and necessary post-translational modifications to become a functional protein used in various biological processes.
Mechanism of Action of Antibiotics That Inhibit Protein Synthesis in Bacteria
Antibiotics that inhibit protein synthesis in bacteria can significantly threaten bacterial survival by disrupting the production of proteins necessary for their survival and reproduction. However, since proteins are also essential for humans, protein synthesis itself must not be indiscriminately inhibited. Therefore, antibiotics that exploit the differences in protein synthesis processes and ribosomes between eukaryotes (such as humans) and prokaryotes (such as bacteria) can inhibit bacteria while relatively minimizing the impact on human cells. Key differences in the protein synthesis processes of eukaryotes and prokaryotes include the use of different ribosomes and variations in the mechanism of translation initiation.
First, eukaryotes and prokaryotes use 80S and 70S ribosomes, respectively, and because there are differences in the structure and composition of these ribosomes, there are antibiotics that target them. A representative example is the tetracycline class of antibiotics. Tetracyclines primarily bind to the 30S subunit of bacterial ribosomes and inhibit protein synthesis by interfering with the binding of aminoacyl-tRNA to the A site during translation. This prevents the proper elongation of the polypeptide chain. Through this mechanism, tetracycline antibiotics inhibit bacterial protein synthesis and are generally classified as bacteriostatic antibiotics that inhibit bacterial growth.
Another example of antibiotics that exploit differences in the translation initiation process are aminoglycoside antibiotics, such as streptomycin. These antibiotics bind to the 30S subunit of the bacterial ribosome and interfere with protein synthesis. In particular, aminoglycosides such as streptomycin not only interfere with the formation of the translation initiation complex but also reduce the accuracy of translation—for example, by causing the mRNA codons to be misread—which can lead to the production of abnormal proteins. Therefore, rather than simply explaining their mechanism as blocking the binding of the translation initiation factor to the initiation tRNA—as described in the original text—it is more accurate to understand that they target the 30S ribosome and interfere with various processes, including translation initiation and translational accuracy. Ultimately, this action prevents bacteria from synthesizing sufficient amounts of normal proteins, thereby inhibiting their growth and reproduction or even killing the bacteria.
