Molecular biology research to benefit patients with Entamoeba histolytica infection

Abstract

SummaryThe development of molecular microbiology has made it possible for us to deepen our understanding of the pathogenesis of amebiasis. Research using the trophozoite form of Entamoeba histolytica has clearly shown us the importance of the interface between the parasite and host cells in vitro. Immunopathogenesis after excystation was similarly well advanced by the use of a novel murine model of amebic colitis. However, it is still challenging to apply these findings to clinical and epidemiological settings. This is mainly because of the lack of a complete infection animal model of amebiasis by oralfecal infection. Moreover, in vitro experiments have predominantly been performed using the same axenic cultured strain HM-1: IMSS isolated about 50 years ago, whereas highly diverse strains are prevalent all over the world. Translational research informed by clinical observations has the greatest potential for the development of effective interventions. Here, we highlight discoveries of the experiments designed from cohort observation and discuss remaining problems to be solved.

An amebic protein disulfide isomerase (PDI) complements the yeast PDI1 mutation but is unable to support cell viability under ER or thermal stress

“…Many of these domains comprise the canonical tetrapeptide CxxC as the active site motif, while some others have a derivative sequence, in which one cysteine was substituted by a selenocysteine, serine, or threonine residue [3]. So far studied, almost all eukaryotic cells contain a PDI family with a diverse domain structure and function, for instance, 21 for human and five in yeast cells [4,5].The pathobiology of the protozoan parasite Entamoeba histolytica, the causative agent of human amebiasis, depends on direct cell contact and secretion of virulence factors [6][7][8]. Although the native conformation of some of the latter is stabilized by disulfide bondsAbbreviations 5-FOA, 5-fluoroorotic acid; ER, endoplasmic reticulum; G-418, geneticin; PDI, protein disulfide isomerase; SD, synthetic dextrose; UPR, unfolded protein response; YPD, yeast extract/peptone/dextrose.…”

“…The pathobiology of the protozoan parasite Entamoeba histolytica, the causative agent of human amebiasis, depends on direct cell contact and secretion of virulence factors [6][7][8]. Although the native conformation of some of the latter is stabilized by disulfide bonds…”

“…The pathobiology of the protozoan parasite Entamoeba histolytica, the causative agent of human amebiasis, depends on direct cell contact and secretion of virulence factors [6][7][8]. Although the native conformation of some of the latter is stabilized by disulfide bonds Abbreviations 5-FOA, 5-fluoroorotic acid; ER, endoplasmic reticulum; G-418, geneticin; PDI, protein disulfide isomerase; SD, synthetic dextrose; UPR, unfolded protein response; YPD, yeast extract/peptone/dextrose.…”

Genome-wide association study reveals genetic link between diarrhea-associatedEntamoeba histolyticainfection and inflammatory bowel disease

“…One possible explanation for the observed heterogeneity in infection rates could be differences in host genetic susceptibility to infection and disease. 10 In a study of preschool age children in Dhaka, Bangladesh, Duggal et al identified a polymorphism in the leptin receptor, rs1137101 resulting in Q223R, was associated with amebiasis when compared to children without this polymorphism. 11 Later work elucidated the mechanism of action of this allele; glutamine at this position led to a decrease in STAT-3-dependent gene expression, which in turn led to an increase in host cell apoptosis during E. histolytica infection.…”

Recent advances in Entamoeba biology: RNA interference, drug discovery, and gut microbiome

“…Consequently, amoebiasis prevalence is higher in developing countries, such as the Indian subcontinent, tropical and central regions of Africa, and South America 11, 12 . However, recent reports also identified amoebic infections in east Asian developed countries and Australia 13– 16 . In developed countries, E. histolytica infection is typically seen in new immigrants and travelers returning from regions where amoebiasis is endemic, and in Japan there is a relatively high incidence of disease in homosexual men 13, 15– 17 .…”