Inhibition of Amebic Lysosomal Acidification Blocks Amebic Trogocytosis and Cell Killing

ABSTRACT Entamoeba histolytica ingests fragments of live host cells in a nibbling-like process termed amebic trogocytosis. Amebic trogocytosis is required for cell killing and contributes to tissue invasion, which is a hallmark of invasive amebic colitis. Work done prior to the discovery of amebic t...

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Autores principales:	Allissia A. Gilmartin, Katherine S. Ralston, William A. Petri
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	Entamoeba histolytica enteric pathogens host-pathogen interactions trogocytosis Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/45b22ea5221b4562a9f635085c21437e
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spelling	oai:doaj.org-article:45b22ea5221b4562a9f635085c21437e2021-11-15T15:51:43ZInhibition of Amebic Lysosomal Acidification Blocks Amebic Trogocytosis and Cell Killing10.1128/mBio.01187-172150-7511https://doaj.org/article/45b22ea5221b4562a9f635085c21437e2017-09-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01187-17https://doaj.org/toc/2150-7511ABSTRACT Entamoeba histolytica ingests fragments of live host cells in a nibbling-like process termed amebic trogocytosis. Amebic trogocytosis is required for cell killing and contributes to tissue invasion, which is a hallmark of invasive amebic colitis. Work done prior to the discovery of amebic trogocytosis showed that acid vesicles are required for amebic cytotoxicity. In the present study, we show that acidified lysosomes are required for amebic trogocytosis and cell killing. Interference with lysosome acidification using ammonium chloride, a weak base, or concanamycin A, a vacuolar H+ ATPase inhibitor, decreased amebic trogocytosis and amebic cytotoxicity. Our data suggest that the inhibitors do not impair the ingestion of an initial fragment but rather block continued trogocytosis and the ingestion of multiple fragments. The acidification inhibitors also decreased phagocytosis, but not fluid-phase endocytosis. These data suggest that amebic lysosomes play a crucial role in amebic trogocytosis, phagocytosis, and cell killing. IMPORTANCE E. histolytica is a protozoan parasite that is prevalent in low-income countries, where it causes potentially fatal diarrhea, dysentery, and liver abscesses. Tissue destruction is a hallmark of invasive E. histolytica infection. The parasite is highly cytotoxic to a wide range of human cells, and parasite cytotoxic activity is likely to drive tissue destruction. E. histolytica is able to kill human cells through amebic trogocytosis. This process also contributes to tissue invasion. Trogocytosis has been observed in other organisms; however, little is known about the mechanism in any system. We show that interference with lysosomal acidification impairs amebic trogocytosis, phagocytosis, and cell killing, indicating that amebic lysosomes are critically important for these processes.Allissia A. GilmartinKatherine S. RalstonWilliam A. PetriAmerican Society for MicrobiologyarticleEntamoeba histolyticaenteric pathogenshost-pathogen interactionstrogocytosisMicrobiologyQR1-502ENmBio, Vol 8, Iss 4 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Entamoeba histolytica enteric pathogens host-pathogen interactions trogocytosis Microbiology QR1-502
spellingShingle	Entamoeba histolytica enteric pathogens host-pathogen interactions trogocytosis Microbiology QR1-502 Allissia A. Gilmartin Katherine S. Ralston William A. Petri Inhibition of Amebic Lysosomal Acidification Blocks Amebic Trogocytosis and Cell Killing
description	ABSTRACT Entamoeba histolytica ingests fragments of live host cells in a nibbling-like process termed amebic trogocytosis. Amebic trogocytosis is required for cell killing and contributes to tissue invasion, which is a hallmark of invasive amebic colitis. Work done prior to the discovery of amebic trogocytosis showed that acid vesicles are required for amebic cytotoxicity. In the present study, we show that acidified lysosomes are required for amebic trogocytosis and cell killing. Interference with lysosome acidification using ammonium chloride, a weak base, or concanamycin A, a vacuolar H+ ATPase inhibitor, decreased amebic trogocytosis and amebic cytotoxicity. Our data suggest that the inhibitors do not impair the ingestion of an initial fragment but rather block continued trogocytosis and the ingestion of multiple fragments. The acidification inhibitors also decreased phagocytosis, but not fluid-phase endocytosis. These data suggest that amebic lysosomes play a crucial role in amebic trogocytosis, phagocytosis, and cell killing. IMPORTANCE E. histolytica is a protozoan parasite that is prevalent in low-income countries, where it causes potentially fatal diarrhea, dysentery, and liver abscesses. Tissue destruction is a hallmark of invasive E. histolytica infection. The parasite is highly cytotoxic to a wide range of human cells, and parasite cytotoxic activity is likely to drive tissue destruction. E. histolytica is able to kill human cells through amebic trogocytosis. This process also contributes to tissue invasion. Trogocytosis has been observed in other organisms; however, little is known about the mechanism in any system. We show that interference with lysosomal acidification impairs amebic trogocytosis, phagocytosis, and cell killing, indicating that amebic lysosomes are critically important for these processes.
format	article
author	Allissia A. Gilmartin Katherine S. Ralston William A. Petri
author_facet	Allissia A. Gilmartin Katherine S. Ralston William A. Petri
author_sort	Allissia A. Gilmartin
title	Inhibition of Amebic Lysosomal Acidification Blocks Amebic Trogocytosis and Cell Killing
title_short	Inhibition of Amebic Lysosomal Acidification Blocks Amebic Trogocytosis and Cell Killing
title_full	Inhibition of Amebic Lysosomal Acidification Blocks Amebic Trogocytosis and Cell Killing
title_fullStr	Inhibition of Amebic Lysosomal Acidification Blocks Amebic Trogocytosis and Cell Killing
title_full_unstemmed	Inhibition of Amebic Lysosomal Acidification Blocks Amebic Trogocytosis and Cell Killing
title_sort	inhibition of amebic lysosomal acidification blocks amebic trogocytosis and cell killing
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/45b22ea5221b4562a9f635085c21437e
work_keys_str_mv	AT allissiaagilmartin inhibitionofamebiclysosomalacidificationblocksamebictrogocytosisandcellkilling AT katherinesralston inhibitionofamebiclysosomalacidificationblocksamebictrogocytosisandcellkilling AT williamapetri inhibitionofamebiclysosomalacidificationblocksamebictrogocytosisandcellkilling
_version_	1718427330869723136

Inhibition of Amebic Lysosomal Acidification Blocks Amebic Trogocytosis and Cell Killing

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