Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Intracellular hypoxia and heat shock response are essential requirements for amoebic pathogenicity and virulence

ABSTRACT: Amongst several amoebic species that colonize the human gut only Entamoeba histolytica is able to cause tissue damage in the intestine and other organs. Amoebic pathogenicity and virulence are commonly evaluated as the parasiteM-+s ability to produce liver abscesses in hamsters (ALAH). Some molecules involved in several functions that enable E. histolytica to invade and survive in the tissues have been identified and proposed as virulence factors. However, despite the fact that during early tissue invasion E. histolytica has to cope with toxic oxygen concentrations, little attention have received the mechanisms of oxygen resistance and its relationship with pathogenicity and virulence. In this work we compared the ability of virulent E. histolytica, non virulent E. histolytica and non pathogenic E. dispar to survive under physiological oxygen concentrations. Also, the effect of hyperoxia on the transcriptome, the oxygen reduction pathway, iron-sulfur protein oxidation, protein carbonylation and complement resistance was analyzed. Our results showed that a low oxygen reduction capacity plus high complement susceptibility contribute to the inability of E. dispar to survive during the early tissue invasion. On the other hand, under hyperoxia, the non virulent E. histolytica phenotype was associated with a defect in the up-regulation of genes of the heat-shock response which correlated with accumulation of oxidized proteins and irreversible PFOR inactivation. We conclude that maintenance of an intracellular hypoxic environment and up regulation of the heat-shock protein response for proper metabolic functioning are primary requirements for amoebic pathogenicity and virulence.

ORGANISM(S): Entamoeba histolytica

SUBMITTER: Nora Hernandez

PROVIDER: E-MTAB-1207 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Entamoeba histolytica is a protozoan parasite that causes colitis and liver abscesses. Several Entamoeba species and strains with differing levels of virulence have been identified. E. histolytica HM-1:IMSS is a virulent strain, E. histolytica Rahman is a nonvirulent strain, and Entamoeba dispar is a nonvirulent species. We used an E. histolytica DNA microarray consisting of 2,110 genes to assess the transcriptional differences between these species/strains with the goal of identifying genes whose expression correlated with a virulence phenotype. We found 415 genes expressed at lower levels in E. dispar and 32 genes with lower expression in E. histolytica Rahman than in E. histolytica HM-1:IMSS. Overall, 29 genes had decreased expression in both the nonvirulent species/strains than the virulent E. histolytica HM-1:IMSS. Interestingly, a number of genes with potential roles in stress response and virulence had decreased expression in either one or both nonvirulent Entamoeba species/strains. These included genes encoding Fe hydrogenase (9.m00419), peroxiredoxin (176.m00112), type A flavoprotein (6.m00467), lysozyme (6.m00454), sphingomyelinase C (29.m00231), and a hypothetical protein with homology to both a Plasmodium sporozoite threonine-asparagine-rich protein (STARP) and a streptococcal hemagglutinin (238.m00054). The function of these genes in Entamoeba and their specific roles in parasite virulence need to be determined. We also found that a number of the non-long-terminal-repeat retrotransposons (EhLINEs and EhSINEs), which have been shown to modulate gene expression and genomic evolution, had lower expression in the nonvirulent species/strains than in E. histolytica HM-1:IMSS. Our results, identifying expression profiles and patterns indicative of a virulence phenotype, may be useful in characterizing the transcriptional framework of virulence. A species experiment design type assays differences between distinct species. Keywords: species_design

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Intracellular hypoxia and heat shock response are essential requirements for amoebic pathogenicity and virulence

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