title: Differential trypanocidal activity of novel macrolide antibiotics; correlation to genetic lineage.
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.
authors.affiliation: Centro de Biología Molecular Severo Ochoa, Universidad Autónoma de Madrid, Campus de Cantoblanco, Madrid, Spain.
authors.forename: Carolina
authors.initials: C
authors.lastname: Aquilino
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Gonzalez Rubio
authors.forename: Elena Maria
authors.initials: EM
authors.lastname: Seco
authors.forename: Leticia
authors.initials: L
authors.lastname: Escudero
authors.forename: Laura
authors.initials: L
authors.lastname: Corvo
authors.forename: Manuel
authors.initials: M
authors.lastname: Soto
authors.forename: Manuel
authors.initials: M
authors.lastname: Fresno
authors.forename: Francisco
authors.initials: F
authors.lastname: Malpartida
authors.forename: Pedro
authors.initials: P
authors.lastname: Bonay
mesh_terms: D000818:Animals; D002463:Cell Membrane Permeability / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D018942:Macrolides / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D050296:Microbial Viability / Q000187:drug effects; D008957:Models, Genetic; D010455:Peptides; D010802:Phylogeny; D014344:Trypanocidal Agents / Q000494:pharmacology* / Q000633:toxicity; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000235:genetics / Q000648:ultrastructure; D014709:Vero Cells
chemical_list: D018942:Macrolides; D010455:Peptides; D014344:Trypanocidal Agents; C085032:IC 101