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Differential trypanocidal activity of novel macrolide antibiotics; correlation to genetic lineage
Authors:Carolina Aquilino  Maria Luisa Gonzalez Rubio  Elena Maria Seco  Leticia Escudero  Laura Corvo  Manuel Soto  Manuel Fresno  Francisco Malpartida  Pedro Bonay
Affiliation:Centro de Biología Molecular "Severo Ochoa", Universidad Autónoma de Madrid, Campus de Cantoblanco, Madrid, Spain.
Abstract:Here we report the systematic study of the anti-trypanocidal activity of some new products derived from S. diastatus on 14 different T. cruzi strains spanning the six genetic lineages of T. cruzi. As the traditional growth inhibition curves giving similar IC(50) showed great differences on antibiotic and lineage tested, we decided to preserve the wealth of information derived from each inhibition curve and used an algorithm related to potency of the drugs, combined in a matrix data set used to generate a cluster tree. The cluster thus generated based just on drug susceptibility data closely resembles the phylogenies of the lineages derived from genetic data and provides a novel approach to correlate genetic data with phenotypes related to pathogenesis of Chagas disease. Furthermore we provide clues on the drugs mechanism of action.
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