Avirulent UG10 Entamoeba histolytica mutant derived from HM-1:IMSS strain shows limited genome variability and aberrant 5-methyl cytosine genomic distribution.

In this study, we aimed to uncover the genome-wide modifications that rendered the avirulent phenotype of the UG10 strain by whole-genome sequencing. As a complementary approach, we conducted Methylated DNA Immunoprecipitation coupled with sequencing (MeDIP-seq) analysis of both, the highly virulent strain, HM1:IMSS, and the low virulence UG10 strain to uncover the genome-wide methylation profile. Both strategies uncovered two aspects of the UG10 avirulent strain. One is the random integration of fragments from the ribosomal gene cluster and tRNA genes, ranging from 120 to 400 bp; and secondly, a clear, enriched methylation profile in the coding and non-coding strand relative to the start codon sequence in genes encoding small GTPases, which is associated with the previously described avirulent phenotype.This study provides the foundation to explore other genetic and epigenetic regulatory circuitries in E. histolytica and novel targets limiting the dissemination of this important pathogen.