[1] Like many of the known natural antibiotics, kasugamycin inhibits proliferation of bacteria by tampering with their ability to make new proteins, the ribosome being the major target.

Recent experiments suggest that kasugamycin indirectly induces dissociation of P-site-bound fMet-tRNAfMet from 30S subunits through perturbation of the mRNA, thereby interfering with translation initiation.

Kasugamycin also induces the formation of unusual 61S ribosomes in vivo, which are proficient in selectively translating leaderless mRNA.

[citation needed] The structure of the kasugamycin-70S ribosome complex from Escherichia coli has been determined by X-ray crystallography at 3.5-A resolution.

The kasugamycin binding sites are present on top of helix 44 (h44), spanning the region between h24 and h28, which contacts the conserved nucleotides A794 and G926.

Instead, kasugamycin mimics the codon nucleotides at the P and E sites by binding within the path of the mRNA, thus perturbing the mRNA-tRNA codon-anticodon interaction.

Spontaneous ksgA mutations conferring a modest level of resistance to kasugamycin occur at a high frequency of 10−6.

[citation needed] Surprisingly, kasugamycin resistance mutations do not inhibit binding of the drug to the ribosome.

Schluenzen, F., Takemoto, C., Wilson, D.N., Kaminishi, T., Harms, J.M., Hanawa-Suetsugu, K., Szaflarski, W., Kawazoe, M., Shirouzu, M., Nierhaus, K.H., et al. (2006).

The antibiotic kasugamycin mimics mRNA nucleotides to destabilize tRNA binding and inhibit canonical translation initiation.

Ochi K., Kim J., Tanaka Y., Wang G., Masuda K., Nanamiya H., Okamoto S., Tokuyama S., Adachi Y. and Kawamura F. (2009).

Inactivation of KsgA, a 16S rRNA Methyltransferase, Causes Vigorous Emergence of Mutants with High-Level Kasugamycin Resistance.