differential trypanocidal activity of novel macrolide antibiotics; correlation to genetic lineage微分trypanocidal活动的新型大环内酯物抗生素;.pdfVIP

Differential Trypanocidal Activity of Novel Macrolide Antibiotics; Correlation to Genetic Lineage 1. 1. 2 2 1 Carolina Aquilino , Maria Luisa Gonzalez Rubio , Elena Maria Seco , Leticia Escudero , Laura Corvo , 1 1 2 1 Manuel Soto , Manuel Fresno , Francisco Malpartida , Pedro Bonay * ´ ´ ´ 1 Centro de Biologıa Molecular ‘‘Severo Ochoa’’, Universidad Autonoma de Madrid, Campus de Cantoblanco, Madrid, Spain, 2 Centro Nacional de Biotecnologıa, 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 IC50 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. Citation: Aquilino C, Gonzalez Rubio ML, Seco EM, Escudero L, Corvo L, et al. (2012) Differential Trypanocidal Activity of Novel Macrolid