What is the mechanism of Capreomycin Sulfate?

Capreomycin sulfate is an important antibiotic used primarily in the treatment of multidrug-resistant tuberculosis (MDR-TB). Understanding the mechanism of action of this drug is crucial for grasping how it combats bacterial infections and why it remains a vital tool in the fight against tuberculosis.

Capreomycin sulfate is a cyclic peptide antibiotic produced by the bacterium Streptomyces capreolus. The drug's primary mechanism of action involves inhibiting protein synthesis within the bacterial cell. It targets the ribosome, which is the molecular machine responsible for constructing proteins based on the genetic instructions encoded in mRNA. This inhibition occurs through several interrelated steps.

Firstly, capreomycin sulfate binds to the 70S ribosome, specifically interacting with both the 30S and 50S subunits. This binding disrupts the normal function of the ribosome, preventing it from effectively synthesizing proteins. In particular, capreomycin interferes with the elongation phase of protein synthesis. During elongation, amino acids are sequentially added to a growing polypeptide chain; capreomycin inhibits this by causing misreading of the mRNA template and by obstructing the translocation of tRNA and mRNA on the ribosome.

Additionally, capreomycin can induce structural changes in the ribosome. These changes hinder the proper alignment and interaction of the ribosomal subunits, further impairing the ribosome's ability to synthesize proteins. Without the ability to produce essential proteins, the bacterial cell cannot maintain critical functions necessary for survival and replication.

Moreover, capreomycin's action is enhanced by its ability to work synergistically with other antibiotics, such as aminoglycosides and tuberactinomycins. This synergistic effect can lead to a more effective disruption of bacterial protein synthesis and, consequently, a higher rate of bacterial cell death.

Resistance to capreomycin can occur, typically through mutations in ribosomal RNA or ribosomal proteins that reduce the drug's binding affinity. However, understanding these resistance mechanisms has guided researchers in developing combination therapies and alternative strategies to overcome resistance.

In summary, capreomycin sulfate exerts its antibacterial effects by targeting the bacterial ribosome and disrupting protein synthesis. This action is critical in treating MDR-TB, making capreomycin an essential component in the arsenal against this persistent and deadly disease. Understanding its mechanism not only provides insights into its therapeutic application but also informs ongoing efforts to combat antibiotic resistance.