Maintenance of intracellular hypoxia and adequate heat shock response are essential requirements for pathogenicity and virulence ofEntamoeba histolytica

Abstract

SummaryAdhesion to cells, cytotoxicity and proteolysis are functions required for virulence and pathogenicity of Entamoeba histolytica. However, there was no correlation between these in vitro functions and the early elimination of non-pathogenic E. dispar and non-virulent E. histolytica (nvEh) in experimental amoebic liver abscesses developed in hamsters. Thus, additional functions may be involved in amoebic pathogenicity and virulence. In the present study, an integral experimental assessment, including innovative technologies for analyses of amoebal pathophysiology, cell biology, biochemistry and transcriptomics, was carried out to elucidate whether other cellular processes are involved in amoebal pathogenicity and virulence. In comparison with virulent E. histolytica, the data indicated that the main reasons for the early clearance of nvEh from hamster liver are decreased intracellular H 2O2 detoxification rate and deficient heat shock protein expression, whereas for E. dispar, it is a relatively lower capacity for O2 reduction. Therefore, maintenance of an intracellular hypoxic environment combined with the induction of an adequate parasite response to oxidative stress are essential requirements for Entamoeba survival in the liver, and therefore for pathogenicity.

Phosphorylation of Eukaryotic Initiation Factor-2α during Stress and Encystation in Entamoeba Species

“…The ability of the parasite to respond to oxidative stress is critical for virulence functions [reviewed in 27] including the pathogen’s ability to survive in host liver [28]. The observation that eIF2α becomes phosphorylated during oxidative stress in E .…”

Chemical Tools to Investigate Mechanisms Associated with HSP90 and HSP70 in Disease

“…It highlighted an unconventional role for HSP70 in the localization of a key regulatory protein at the leading edges of cancer cells and the important consequences that this holds for their ability to migrate (Boroughs et al, 2011). Others used VER155008 to investigate stress granule formation (Bounedjah et al, 2014), the pathogenicity and virulence of Entamoeba histolytica (Santos et al, 2015) to confirm a role for HSP70 in the infection cycle of baculoviruses. When VER-155008 was added early in infection, the synthesis of viral proteins, genome replication and the production of budded virions were markedly inhibited by the chemical tool indicating the dependence of virus reproduction on HSP70 (Lyupina et al, 2014).…”

Entamoeba histolytica: Quantitative Proteomics Analysis Reveals Putative Virulence-Associated Differentially Abundant Membrane Proteins

“…The virulence of the vEh trophozoites was maintained by periodically recovering them from amebic liver abscess of infected hamsters according to the protocol from Olivos et al 16 Meanwhile, the avEh trophozoites were vEh trophozoites that lost the ability to cause amebic liver abscess because of the long-term in vitro maintenance of the culture (> 18 years). 16,17 Membrane protein extraction. The membrane proteins of vEh and avEh trophozoites were extracted using the ProteoExtract ™ Native Membrane Protein Extraction kit (Calbiochem, San Diego, CA) according to the manufacturer's protocol.…”