MECHANISM OF ACTION

Hygromycin B is an aminocyclitol antibiotic with broad spectrum activity against prokaryotes and eukaryotes (1,2). Hygromycin B strongly inhibits protein synthesis through a dual effect on mRNA translation (3,4). Like other aminoglycoside antibiotics, hygromycin B induces misreading of aminoacyl-tRNA by distorting the ribosomal A site (decoding center) (3,5,6,7). Hygromycin B also affects the ribosomal translocation process (3,8,9). In the presence of the antibiotic, mRNA is often mistranslocated, being moved more or less than the three necessary bases.

 

References

  1. Pettinger R. C., Wolfe R. N., Hoehn M. M., Marks P. N., Dailey W. A. and McGuire J. M. (1953). Hygromycin I. Preliminary studies on the production and biological activity of a new antibiotic. Antibiot. Chemother. 3, 1268-1278.
  2. Bakker EP. (1992) Aminoglycoside and aminocyclitol antibiotics: hygromycin B is an atypical bactericidal compound that exerts effects on cells of Escherichia coli characteristics for bacteriostatic aminocyclitols. J Gen Microbiol. 138 ( Pt 3):563-9.
  3. Cabanas MJ, Vazquez D, Modolell J. (1978) Dual interference of hygromycin B with ribosomal translocation and with aminoacyl-tRNA recognition. Eur J Biochem. 87(1):21-27
  4. Lacal JC, Carrasco L. (1983) Antiviral effects of hygromycin B, a translation inhibitor nonpermeant to uninfected cells. Antimicrob Agents Chemother 24(2):273-5.
  5. Davies J, Davis BD (1968) Misreading of ribonucleic acid code words induced by aminoglycoside antibiotics. The effect of drug concentration.J Biol Chem. 243(12):3312-6.
  6. Moazed, D. and H.F. Noller (1987) Interaction of antibiotics with functional sites in 16S ribosomal RNA. Nature 327(6121): 389-94.
  7. Spahn, C.M. and C.D. Prescott (1996) Throwing a spanner in the works: antibiotics and the translation apparatus. J Mol Med 74(8): 423-39.
  8. Gonzalez A, Jimenez A, Vazquez D, Davies JE, Schindler D (1978) Studies on the mode of action of hygromycin B, an inhibitor of translocation in eukaryotes.Biochim Biophys Acta. 521(2):459-69.
  9. Hausner TP, Geigenmuller U, Nierhaus KH. (1988) The allosteric three-site model for the ribosomal elongation cycle. New insights into the inhibition mechanisms of aminoglycosides, thiostrepton, and viomycin.J Biol Chem. 263(26):13103-11.