G protein signaling in the parasite Entamoeba histolytica

The parasite Entamoeba histolytica causes amebic colitis and systemic amebiasis. Among the known amebic factors contributing to pathogenesis are signaling pathways involving heterotrimeric and Ras superfamily G proteins. Here, we review the current knowledge of the roles of heterotrimeric G protein subunits, Ras, Rho and Rab GTPase families in E. histolytica pathogenesis, as well as of their downstream signaling effectors and nucleotide cycle regulators. Heterotrimeric G protein signaling likely modulates amebic motility and attachment to and killing of host cells, in part through activation of an RGS-RhoGEF (regulator of G protein signaling-Rho guanine nucleotide exchange factor) effector. Rho family GTPases, as well as RhoGEFs and Rho effectors (formins and p21-activated kinases) regulate the dynamic actin cytoskeleton of E. histolytica and associated pathogenesis-related cellular processes, such as migration, invasion, phagocytosis and evasion of the host immune response by surface receptor capping. A remarkably large family of 91 Rab GTPases has multiple roles in a complex amebic vesicular trafficking system required for phagocytosis and pinocytosis and secretion of known virulence factors, such as amebapores and cysteine proteases. Although much remains to be discovered, recent studies of G protein signaling in E. histolytica have enhanced our understanding of parasitic pathogenesis and have also highlighted possible targets for pharmacological manipulation.

Molecular mechanisms of pathogenesis in amebiasis.

Though both Entamoeba histolytica and E. dispar colonize the human gut, only the former is capable of invading tissues and causing disease. Although the biology of the parasite and the mechanism of pathogenesis have been intensively studied, there is a lack of consensus about the molecules of E. histolytica that actively participate in pathogenesis. This article reviews some key molecules involved. Ga1NAc-inhibitable adhesin is a membrane-associated glycoprotein nature, consisting of heavy and light subunits; each of these is encoded by multiple genes. The heavy subunit is useful in differentiating E. histolytica from E. dispar. Three structurally similar isoforms of amebapore, A, B and C, have been identified in E. histolytica but C is absent in E. dispar. Proteolytic enzymes such as collagenase and cysteine proteinases and cytolytic enzymes like phospholipase A are important. Collagenase activity is mainly accumulated in electron-dense granules. Cysteine proteinase is encoded by six genes, of which EhCP5 is exclusively present in E. histolytica.

Amebiasis / Amebiasis

La amebiasis es una enfermedad parasitaria endémica causada por el protozoario conocido como Entamoeba histolytica. Existen otras amebas que parasitan al hombre pero E. histolytica es la única patógena. No obstante que la amebiasis a menudo es considerada enfermedad tropical, pues no hay duda que su frecuencia es más elevada en regiones con clima cálido y húmedo, ha sido observada prácticamente en todas las latitudes