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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Membrane Permeability / drug effects
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Cell Survival / drug effects
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Chlorocebus aethiops
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Macrolides / pharmacology*
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Membrane Potential, Mitochondrial / drug effects
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Microbial Viability / drug effects
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Models, Genetic
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Peptides
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Phylogeny
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Trypanocidal Agents / pharmacology*
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Trypanocidal Agents / toxicity
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Trypanosoma cruzi / drug effects*
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Trypanosoma cruzi / genetics
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Trypanosoma cruzi / ultrastructure
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Vero Cells
Substances
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Macrolides
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Peptides
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Trypanocidal Agents
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IC 101
Grants and funding
This work was supported by Fondo de Investigaciones Sanitarias-Ministerio de Sanidad (FIS-PI08/0960) to PB and (FIS-PI08/0101) to MS; ChagasEpiNet (European VII framework Program) to MF; and Network RICET (Red Investigacion Cooperativa en Enfermedades Tropicales) from the FIS (Fondo de Investigaciones Sanitarias), Ministerio de Sanidad. Institutional support from Fundacion Ramon Areces. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.