<italic toggle="yes">Giardia</italic> Colonizes and Encysts in High-Density Foci in the Murine Small Intestine

ABSTRACT Giardia lamblia is a highly prevalent yet understudied protistan parasite causing significant diarrheal disease worldwide. Hosts ingest Giardia cysts from contaminated sources. In the gastrointestinal tract, cysts excyst to become motile trophozoites, colonizing and attaching to the gut epi...

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Autores principales:	N. R. Barash, C. Nosala, J. K. Pham, S. G. McInally, S. Gourguechon, B. McCarthy-Sinclair, S. C. Dawson
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	Giardia bioluminescence encystation parasite pathogenesis Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/fbef55bbf30a4dd0a868ab41859d928a
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spelling	oai:doaj.org-article:fbef55bbf30a4dd0a868ab41859d928a2021-11-15T15:21:46Z<italic toggle="yes">Giardia</italic> Colonizes and Encysts in High-Density Foci in the Murine Small Intestine10.1128/mSphere.00343-162379-5042https://doaj.org/article/fbef55bbf30a4dd0a868ab41859d928a2017-06-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00343-16https://doaj.org/toc/2379-5042ABSTRACT Giardia lamblia is a highly prevalent yet understudied protistan parasite causing significant diarrheal disease worldwide. Hosts ingest Giardia cysts from contaminated sources. In the gastrointestinal tract, cysts excyst to become motile trophozoites, colonizing and attaching to the gut epithelium. Trophozoites later differentiate into infectious cysts that are excreted and contaminate the environment. Due to the limited accessibility of the gut, the temporospatial dynamics of giardiasis in the host are largely inferred from laboratory culture and thus may not mirror Giardia physiology in the host. Here, we have developed bioluminescent imaging (BLI) to directly interrogate and quantify the in vivo temporospatial dynamics of Giardia infection, thereby providing an improved murine model to evaluate anti-Giardia drugs. Using BLI, we determined that parasites primarily colonize the proximal small intestine nonuniformly in high-density foci. By imaging encystation-specific bioreporters, we show that encystation initiates shortly after inoculation and continues throughout the duration of infection. Encystation also initiates in high-density foci in the proximal small intestine, and high density contributes to the initiation of encystation in laboratory culture. We suggest that these high-density in vivo foci of colonizing and encysting Giardia likely result in localized disruption to the epithelium. This more accurate visualization of giardiasis redefines the dynamics of the in vivo Giardia life cycle, paving the way for future mechanistic studies of density-dependent parasitic processes in the host. IMPORTANCE Giardia is a single-celled parasite causing significant diarrheal disease in several hundred million people worldwide. Due to limited access to the site of infection in the gastrointestinal tract, our understanding of the dynamics of Giardia infections in the host has remained limited and largely inferred from laboratory culture. To better understand Giardia physiology and colonization in the host, we developed imaging methods to quantify Giardia expressing bioluminescent physiological reporters in two relevant animal models. We discovered that parasites primarily colonize and encyst in the proximal small intestine in discrete, high-density foci. We also show that high parasite density contributes to encystation initiation.N. R. BarashC. NosalaJ. K. PhamS. G. McInallyS. GourguechonB. McCarthy-SinclairS. C. DawsonAmerican Society for MicrobiologyarticleGiardiabioluminescenceencystationparasitepathogenesisMicrobiologyQR1-502ENmSphere, Vol 2, Iss 3 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Giardia bioluminescence encystation parasite pathogenesis Microbiology QR1-502
spellingShingle	Giardia bioluminescence encystation parasite pathogenesis Microbiology QR1-502 N. R. Barash C. Nosala J. K. Pham S. G. McInally S. Gourguechon B. McCarthy-Sinclair S. C. Dawson <italic toggle="yes">Giardia</italic> Colonizes and Encysts in High-Density Foci in the Murine Small Intestine
description	ABSTRACT Giardia lamblia is a highly prevalent yet understudied protistan parasite causing significant diarrheal disease worldwide. Hosts ingest Giardia cysts from contaminated sources. In the gastrointestinal tract, cysts excyst to become motile trophozoites, colonizing and attaching to the gut epithelium. Trophozoites later differentiate into infectious cysts that are excreted and contaminate the environment. Due to the limited accessibility of the gut, the temporospatial dynamics of giardiasis in the host are largely inferred from laboratory culture and thus may not mirror Giardia physiology in the host. Here, we have developed bioluminescent imaging (BLI) to directly interrogate and quantify the in vivo temporospatial dynamics of Giardia infection, thereby providing an improved murine model to evaluate anti-Giardia drugs. Using BLI, we determined that parasites primarily colonize the proximal small intestine nonuniformly in high-density foci. By imaging encystation-specific bioreporters, we show that encystation initiates shortly after inoculation and continues throughout the duration of infection. Encystation also initiates in high-density foci in the proximal small intestine, and high density contributes to the initiation of encystation in laboratory culture. We suggest that these high-density in vivo foci of colonizing and encysting Giardia likely result in localized disruption to the epithelium. This more accurate visualization of giardiasis redefines the dynamics of the in vivo Giardia life cycle, paving the way for future mechanistic studies of density-dependent parasitic processes in the host. IMPORTANCE Giardia is a single-celled parasite causing significant diarrheal disease in several hundred million people worldwide. Due to limited access to the site of infection in the gastrointestinal tract, our understanding of the dynamics of Giardia infections in the host has remained limited and largely inferred from laboratory culture. To better understand Giardia physiology and colonization in the host, we developed imaging methods to quantify Giardia expressing bioluminescent physiological reporters in two relevant animal models. We discovered that parasites primarily colonize and encyst in the proximal small intestine in discrete, high-density foci. We also show that high parasite density contributes to encystation initiation.
format	article
author	N. R. Barash C. Nosala J. K. Pham S. G. McInally S. Gourguechon B. McCarthy-Sinclair S. C. Dawson
author_facet	N. R. Barash C. Nosala J. K. Pham S. G. McInally S. Gourguechon B. McCarthy-Sinclair S. C. Dawson
author_sort	N. R. Barash
title	<italic toggle="yes">Giardia</italic> Colonizes and Encysts in High-Density Foci in the Murine Small Intestine
title_short	<italic toggle="yes">Giardia</italic> Colonizes and Encysts in High-Density Foci in the Murine Small Intestine
title_full	<italic toggle="yes">Giardia</italic> Colonizes and Encysts in High-Density Foci in the Murine Small Intestine
title_fullStr	<italic toggle="yes">Giardia</italic> Colonizes and Encysts in High-Density Foci in the Murine Small Intestine
title_full_unstemmed	<italic toggle="yes">Giardia</italic> Colonizes and Encysts in High-Density Foci in the Murine Small Intestine
title_sort	<italic toggle="yes">giardia</italic> colonizes and encysts in high-density foci in the murine small intestine
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/fbef55bbf30a4dd0a868ab41859d928a
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<italic toggle="yes">Giardia</italic> Colonizes and Encysts in High-Density Foci in the Murine Small Intestine

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