What is the mechanism of Streptomycin Sulfate?

Streptomycin sulfate is a well-known antibiotic that belongs to the aminoglycoside class. Its primary mechanism of action is associated with its ability to inhibit bacterial protein synthesis, leading to the eventual death of the bacteria. To understand how streptomycin sulfate achieves this, it is important to delve into the detailed steps of its interaction with the bacterial ribosome.

Streptomycin sulfate targets the 30S subunit of the bacterial ribosome, a complex molecular machine responsible for translating genetic information into proteins. Specifically, streptomycin binds to a region in the 16S rRNA of the 30S subunit. This binding disrupts the normal function of the ribosome in several ways. Firstly, streptomycin interferes with the initiation complex of protein synthesis. By preventing the proper binding of formylmethionine-tRNA to the ribosome, it hinders the formation of the initiation complex, which is essential for the accurate start of protein translation.

Furthermore, streptomycin causes misreading of mRNA. The antibiotic induces conformational changes in the ribosome that lead to incorrect codon-anticodon pairing during the elongation phase of protein synthesis. As a result, the ribosome incorporates incorrect amino acids into the growing polypeptide chain, producing nonfunctional or toxic proteins. This accumulation of faulty proteins can disrupt various cellular processes, ultimately leading to cell death.

Streptomycin's action is particularly effective against aerobic Gram-negative bacteria, although it also exhibits activity against some Gram-positive bacteria and Mycobacterium tuberculosis, the causative agent of tuberculosis. The effectiveness of streptomycin is heightened by its ability to penetrate the bacterial cell envelope and reach its target within the cytoplasm. However, bacterial resistance to streptomycin can occur through various mechanisms. One common resistance mechanism involves mutations in the rpsL gene, which encodes the ribosomal protein S12. These mutations reduce the binding affinity of streptomycin to the ribosome, diminishing its inhibitory effects.

Another resistance mechanism includes the modification of 16S rRNA by methyltransferases, which alter the binding site of streptomycin, rendering it ineffective. Bacteria can also acquire resistance through the enzymatic inactivation of streptomycin by aminoglycoside-modifying enzymes such as adenylyltransferases, acetyltransferases, and phosphotransferases. These enzymes chemically modify streptomycin, preventing it from binding to the ribosome.

Despite these resistance mechanisms, streptomycin sulfate remains a valuable tool in the treatment of various bacterial infections. It is often used in combination with other antibiotics to enhance its efficacy and reduce the likelihood of resistance development. In tuberculosis treatment, streptomycin is typically used as part of a multi-drug regimen to ensure comprehensive eradication of the mycobacteria.

In summary, streptomycin sulfate exerts its antibacterial effects by binding to the 30S subunit of the bacterial ribosome, disrupting protein synthesis through the misreading of mRNA and the prevention of proper initiation complex formation. While resistance mechanisms can undermine its effectiveness, streptomycin continues to play a crucial role in combating bacterial infections, particularly when used in combination with other antibiotics. Understanding the precise mechanisms of streptomycin action and resistance is essential for optimizing its use and developing new strategies to overcome bacterial resistance.