Question

Many antibiotics are effective as drugs to fight off bacterial infections because they inhibit protein synthesis in bacterial cells. Using the information provided in the following table that highlights several antibiotics and their mode of action, discuss which phase of translation is inhibited: initiation, elongation, or termìnation. What other components of the translational machinery could be targeted to inhibit bacterial protein synthesis? $$\begin{array}{ll} \text { Antibiotic } & \text { Action } \\ \text { 1. Streptomycin } & \text { Binds to 30S ribosomal subunit } \\ \text { 2. Chloramphenicol } & \text { Inhibits peptidyl transferase of } \\ & \text { 70S ribosome } \\ \text { 3. Tetracycline } & \text { Inhibits binding of charged tRNA to } \\ \text { 4. Erythromycin } & \text { Binds to free 50S particle and pre- } \\ & \text { vents formation of 70S ribosome } \\ \text { 5. Kasugamycin } & \text { Inhibits binding of tRNA }^{\text {fllet }} \\\ \text { 6. Thiostrepton } & \text { Prevents translocation by } \\ & \text { inhibiting EF-G } \\\\\hline\end{array}$$

Short answer

Short Answer: The antibiotics mentioned above inhibit different phases of translation: Streptomycin, Erythromycin, and Kasugamycin interfere with initiation; Chloramphenicol, Tetracycline, and Thiostrepton interfere with elongation. Other potential targets in the translational machinery to inhibit bacterial protein synthesis could include aminoacyl-tRNA synthetases, initiation factors (IF-1, IF-2, IF-3), elongation factors (EF-Tu, EF-Ts), and the ribosome recycling factor (RRF).

Step-by-step solution

Determine the affected phase by each antibiotic

To determine which phase of translation is inhibited by each antibiotic, let's analyze their mode of action: 1. Streptomycin: Binds to 30S ribosomal subunit - This action interferes with the initiation phase of translation. 2. Chloramphenicol: Inhibits peptidyl transferase of 70S ribosome - This action interferes with the elongation phase of translation. 3. Tetracycline: Inhibits binding of charged tRNA - This action interferes with the elongation phase of translation. 4. Erythromycin: Binds to free 50S particle and prevents formation of 70S ribosome - This action interferes with the initiation phase of translation. 5. Kasugamycin: Inhibits binding of tRNA^met - This action interferes with the initiation phase of translation. 6. Thiostrepton: Prevents translocation by inhibiting EF-G (elongation factor) - This action interferes with the elongation phase of translation.

Discuss other potential targets in the translational machinery

Besides the targets mentioned above, other components of the translational machinery that could be targeted to inhibit bacterial protein synthesis include: 1. Aminoacyl-tRNA synthetases: These enzymes play a crucial role in charging tRNAs with their corresponding amino acids. Inhibiting these enzymes would prevent the formation of charged tRNAs, thereby stopping protein synthesis. 2. Initiation factors: Bacterial initiation factors like IF-1, IF-2, and IF-3 play essential roles in the formation of the initiation complex. Inhibiting these factors would disrupt the formation of this complex, stopping protein synthesis at the initiation phase. 3. Elongation factors: Besides EF-G (targeted by Thiostrepton), other elongation factors like EF-Tu and EF-Ts could also be potential targets. These factors are responsible for carrying charged tRNAs to the ribosome and helping the tRNAs maintain their charged state. Inhibiting these factors would prevent tRNAs from delivering amino acids to the ribosome, stopping protein synthesis at the elongation phase. 4. Ribosome recycling factor (RRF): This factor is responsible for disassembling the ribosome at the end of the termination phase. Inhibiting RRF would prevent the ribosome from being reused for further translation, reducing protein synthesis efficiency.

Key concepts

Bacterial Protein Synthesis

In understanding how antibiotics can disrupt bacterial protein synthesis, it is crucial to comprehend the basics of this biological process. Bacterial protein synthesis involves translating genetic code into proteins, molecules vital for almost all cell functions. This process occurs in the cytoplasm on structures called ribosomes, which are made up of two subunits - generally referred to as the small and large subunits in bacteria, these correspond to the 30S and 50S fractions respectively, together forming the functional 70S ribosome.

The synthesis consists of three primary phases: initiation, where the ribosomal subunits assemble around the messenger RNA (mRNA); elongation, where amino acids are sequentially added to a growing polypeptide chain; and termination, where the finished protein is released, and the ribosome disassembles. Disruption of any of these phases by antibiotics can hinder the bacteria's ability to synthesize proteins, an action that proves lethal or inhibitory for bacterial growth and survival.

Through the exercise, we see examples such as streptomycin, kasugamycin and erythromycin interfering with the initiation phase, while chloramphenicol, tetracycline and thiostrepton interfere with the elongation phase. Knowing which phase is targeted by an antibiotic is essential for understanding its therapeutic effects and potential side reactions.

Ribosomal Subunits and Antibiotics

Antibiotics operate by selectively targeting bacterial cells while causing minimal damage to human cells. One way they achieve this is by attacking the ribosomal subunits unique to bacteria. For example, streptomycin binds to the 30S subunit, affecting the ribosome's ability to correctly initiate protein synthesis. Similarly, erythromycin's binding to the 50S subunit prevents the formation of the 70S initiation complex, crucial for starting protein synthesis.

Distinguishing Ribosomal Subunits

Eukaryotic cells, including human cells, have 80S ribosomes (made up of 40S and 60S subunits), differing from the bacterial 70S ribosomes. This differential structure is what many antibiotics exploit, allowing them to selectively inhibit bacterial protein synthesis without affecting eukaryotic cells.

This knowledge is key when developing or using antibiotics, as it provides a pathway to target bacteria without harming the host. Furthermore, understanding these mechanisms can drive the evolution of new drugs to combat antibiotic resistance, an increasing global challenge.

Translation Phases Inhibition

Inhibition of any phase within the protein translation process can be catastrophic for bacterial survival. Let's dive into the intricacies of these phases and explore how antibiotics can disrupt them.

Initiation Phase

During the initiation phase, any interference with the formation of the 70S ribosome or the binding of the initiator tRNA can halt protein synthesis before it even begins. Antibiotics like streptomycin, kasugamycin, and erythromycin impair this phase by different mechanisms, preventing the ribosome from correctly interpreting the mRNA template.

Elongation Phase

In the elongation phase, antibiotics such as chloramphenicol, tetracycline, and thiostrepton play a crucial role. They target specific interactions or enzymes like the peptidyl transferase center and elongation factors, disrupting the addition of new amino acids and preventing the proper growth of the polypeptide chain.

Exploiting the vulnerability of the bacterial ribosome through these targeted approaches not only provides a potent avenue for antimicrobial therapy but also underscores the value in developing new antibiotics that can circumvent the mechanisms bacteria use to develop resistance.