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Sensitivity of Kinetoplastids to aminoglycoside: Correlation with 3' small subunit rRNA gene

Masoom Yasinzai, A.S.Hamad Elgazwy

In-vitro culture systems were used to assess the growth inhibition of Kinetopasids by a variety of aminoglycosides. The parasites were allowed to grow to the stationary phase in the presence of varying concentrations of the drug. The IC-50 for every drug was calculated by its comparison with the control. The sensitivity of various leishmanial starins to these drugs is in the order G418>Hygromycin>Paromomycin >Neomycin. However under our assay conditions Gentamycin and Kanamycin were nonleishmanicidal. The effect of the drug on the intracellular formof the parasite in the macrophage cell line was also tested. Other Kinetoplastids, such as crithidia spp.And Blastocrithida culiciswere tested which showed resistance to all these drugs. Secondary structures for the 3Â’ region of the ssurRNA genes for these organisms were constructed, and the correlation between the drug sensitivity and the secondary structures is presented. In leishmania it is a T-Apair in the secondary structure instead of C-G at position 1409-1491 (E.coli) as reported in the other organisms which is responsible for paromomycin sensitivity. The residue responsible for hygromycin sensitivity remained as G(1494). The 3Â’ loopstemU- structures are different for organisms in this family, whichmight be of significance in determining the overall sensitivity to these aminoglycosides. This might provide rational approaches to the development of drugs specific for leishmania. Because of the sensitivity of mammalian cells to this drug, we suggest that paromomycin may used for testing leishmaniasis.