This pathway illustrates the multifaceted interactions between streptomycin—an aminoglycoside antibiotic—and Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv), highlighting its antibacterial mechanism, molecular targets, and downstream cellular consequences. Once inside the cytoplasm, streptomycin binds to the 16S rRNA component of the 30S ribosomal subunit, specifically interacting with the S12 protein and the decoding site of the ribosome. This interaction alters ribosomal conformation, leading to misreading of mRNA codons and premature termination of peptide synthesis. At the molecular interaction level, the antibiotic’s binding interferes with the fidelity of translation and promotes the incorporation of incorrect amino acids, producing nonfunctional or toxic proteins. These aberrant proteins can integrate into the bacterial membrane, increasing permeability and further enhancing streptomycin uptake—creating a self-amplifying bactericidal effect. At the cellular outcome level, inhibition of accurate protein synthesis leads to loss of metabolic integrity, disruption of essential enzymatic systems, and eventual cell death. In Mycobacterium tuberculosis, streptomycin is particularly effective against actively dividing cells, though its efficacy diminishes against nonreplicating or intracellular bacilli due to limited penetration and lower metabolic activity. Host pharmacodynamics reflect streptomycin’s poor oral absorption and reliance on parenteral administration. In humans, the drug distributes primarily in extracellular fluids and is excreted unchanged via the kidneys. Ototoxicity and nephrotoxicity are notable dose-limiting adverse effects, arising from accumulation in cochlear and renal tissues. Together, this pathway represents the molecular cascade by which streptomycin exerts its bactericidal action—binding to the ribosome, corrupting protein synthesis, and destabilizing cellular function—while also illustrating the bacterial adaptations that modulate drug sensitivity during tuberculosis therapy.

Streptomycin Tuberculosis Pathway References