Genomic analysis of Colombian Leishmania panamensis strains with different level of virulence

Daniel Alfonso Urrea, Jorge Duitama, Hideo Imamura, Juan F Álzate, Juanita Gil, Natalia Muñoz, Janny Alexander Villa, Jean-Claude Dujardin, José R Ramirez-Pineda, Omar Triana-Chavez

Research output: Contribution to journalA1: Web of Science-article

3 Downloads (Pure)

Abstract

The establishment of Leishmania infection in mammalian hosts and the subsequent manifestation of clinical symptoms require internalization into macrophages, immune evasion and parasite survival and replication. Although many of the genes involved in these processes have been described, the genetic and genomic variability associated to differences in virulence is largely unknown. Here we present the genomic variation of four Leishmania (Viannia) panamensis strains exhibiting different levels of virulence in BALB/c mice and its application to predict novel genes related to virulence. De novo DNA sequencing and assembly of the most virulent strain allowed comparative genomics analysis with sequenced L. (Viannia) panamensis and L. (Viannia) braziliensis strains, and showed important variations at intra and interspecific levels. Moreover, the mutation detection and a CNV search revealed both base and structural genomic variation within the species. Interestingly, we found differences in the copy number and protein diversity of some genes previously related to virulence. Several machine-learning approaches were applied to combine previous knowledge with features derived from genomic variation and predict a curated set of 66 novel genes related to virulence. These genes can be prioritized for validation experiments and could potentially become promising drug and immune targets for the development of novel prophylactic and therapeutic interventions.

Original languageEnglish
JournalScientific Reports
Volume8
Issue number1
Pages (from-to)17336
Number of pages16
ISSN2045-2322
DOIs
Publication statusPublished - 2018

Fingerprint Dive into the research topics of 'Genomic analysis of Colombian <em>Leishmania panamensis</em> strains with different level of virulence'. Together they form a unique fingerprint.

Cite this