Neonatal Mouse Gut Metabolites Influence <named-content content-type="genus-species">Cryptosporidium parvum</named-content> Infection in Intestinal Epithelial Cells

ABSTRACT The protozoan parasite Cryptosporidium sp. is a leading cause of diarrheal disease in those with compromised or underdeveloped immune systems, particularly infants and toddlers in resource-poor localities. As an enteric pathogen, Cryptosporidium sp. invades the apical surface of intestinal...

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Autores principales:	Kelli L. VanDussen, Lisa J. Funkhouser-Jones, Marianna E. Akey, Deborah A. Schaefer, Kevin Ackman, Michael W. Riggs, Thaddeus S. Stappenbeck, L. David Sibley
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	16S rRNA Cryptosporidium parvum enteric infection essential nutrient fatty acid metabolite Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/15ba3df73dfa42048c217995bef69455
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spelling	oai:doaj.org-article:15ba3df73dfa42048c217995bef694552021-11-15T15:55:44ZNeonatal Mouse Gut Metabolites Influence <named-content content-type="genus-species">Cryptosporidium parvum</named-content> Infection in Intestinal Epithelial Cells10.1128/mBio.02582-202150-7511https://doaj.org/article/15ba3df73dfa42048c217995bef694552020-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02582-20https://doaj.org/toc/2150-7511ABSTRACT The protozoan parasite Cryptosporidium sp. is a leading cause of diarrheal disease in those with compromised or underdeveloped immune systems, particularly infants and toddlers in resource-poor localities. As an enteric pathogen, Cryptosporidium sp. invades the apical surface of intestinal epithelial cells, where it resides in close proximity to metabolites in the intestinal lumen. However, the effect of gut metabolites on susceptibility to Cryptosporidium infection remains largely unstudied. Here, we first identified which gut metabolites are prevalent in neonatal mice when they are most susceptible to Cryptosporidium parvum infection and then tested the isolated effects of these metabolites on C. parvum invasion and growth in intestinal epithelial cells. Our findings demonstrate that medium or long-chain saturated fatty acids inhibit C. parvum growth, perhaps by negatively affecting the streamlined metabolism in C. parvum, which is unable to synthesize fatty acids. Conversely, long-chain unsaturated fatty acids enhanced C. parvum invasion, possibly by modulating membrane fluidity. Hence, gut metabolites, either from diet or produced by the microbiota, influence C. parvum growth in vitro and may also contribute to the early susceptibility to cryptosporidiosis seen in young animals. IMPORTANCE Cryptosporidium sp. occupies a unique intracellular niche that exposes the parasite to both host cell contents and the intestinal lumen, including metabolites from the diet and produced by the microbiota. Both dietary and microbial products change over the course of early development and could contribute to the changes seen in susceptibility to cryptosporidiosis in humans and mice. Consistent with this model, we show that the immature gut metabolome influenced the growth of Cryptosporidium parvum in vitro. Interestingly, metabolites that significantly altered parasite growth were fatty acids, a class of molecules that Cryptosporidium sp. is unable to synthesize de novo. The enhancing effects of polyunsaturated fatty acids and the inhibitory effects of saturated fatty acids presented in this study may provide a framework for future studies into this enteric parasite’s interactions with exogenous fatty acids during the initial stages of infection.Kelli L. VanDussenLisa J. Funkhouser-JonesMarianna E. AkeyDeborah A. SchaeferKevin AckmanMichael W. RiggsThaddeus S. StappenbeckL. David SibleyAmerican Society for Microbiologyarticle16S rRNACryptosporidium parvumenteric infectionessential nutrientfatty acidmetaboliteMicrobiologyQR1-502ENmBio, Vol 11, Iss 6 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	16S rRNA Cryptosporidium parvum enteric infection essential nutrient fatty acid metabolite Microbiology QR1-502
spellingShingle	16S rRNA Cryptosporidium parvum enteric infection essential nutrient fatty acid metabolite Microbiology QR1-502 Kelli L. VanDussen Lisa J. Funkhouser-Jones Marianna E. Akey Deborah A. Schaefer Kevin Ackman Michael W. Riggs Thaddeus S. Stappenbeck L. David Sibley Neonatal Mouse Gut Metabolites Influence <named-content content-type="genus-species">Cryptosporidium parvum</named-content> Infection in Intestinal Epithelial Cells
description	ABSTRACT The protozoan parasite Cryptosporidium sp. is a leading cause of diarrheal disease in those with compromised or underdeveloped immune systems, particularly infants and toddlers in resource-poor localities. As an enteric pathogen, Cryptosporidium sp. invades the apical surface of intestinal epithelial cells, where it resides in close proximity to metabolites in the intestinal lumen. However, the effect of gut metabolites on susceptibility to Cryptosporidium infection remains largely unstudied. Here, we first identified which gut metabolites are prevalent in neonatal mice when they are most susceptible to Cryptosporidium parvum infection and then tested the isolated effects of these metabolites on C. parvum invasion and growth in intestinal epithelial cells. Our findings demonstrate that medium or long-chain saturated fatty acids inhibit C. parvum growth, perhaps by negatively affecting the streamlined metabolism in C. parvum, which is unable to synthesize fatty acids. Conversely, long-chain unsaturated fatty acids enhanced C. parvum invasion, possibly by modulating membrane fluidity. Hence, gut metabolites, either from diet or produced by the microbiota, influence C. parvum growth in vitro and may also contribute to the early susceptibility to cryptosporidiosis seen in young animals. IMPORTANCE Cryptosporidium sp. occupies a unique intracellular niche that exposes the parasite to both host cell contents and the intestinal lumen, including metabolites from the diet and produced by the microbiota. Both dietary and microbial products change over the course of early development and could contribute to the changes seen in susceptibility to cryptosporidiosis in humans and mice. Consistent with this model, we show that the immature gut metabolome influenced the growth of Cryptosporidium parvum in vitro. Interestingly, metabolites that significantly altered parasite growth were fatty acids, a class of molecules that Cryptosporidium sp. is unable to synthesize de novo. The enhancing effects of polyunsaturated fatty acids and the inhibitory effects of saturated fatty acids presented in this study may provide a framework for future studies into this enteric parasite’s interactions with exogenous fatty acids during the initial stages of infection.
format	article
author	Kelli L. VanDussen Lisa J. Funkhouser-Jones Marianna E. Akey Deborah A. Schaefer Kevin Ackman Michael W. Riggs Thaddeus S. Stappenbeck L. David Sibley
author_facet	Kelli L. VanDussen Lisa J. Funkhouser-Jones Marianna E. Akey Deborah A. Schaefer Kevin Ackman Michael W. Riggs Thaddeus S. Stappenbeck L. David Sibley
author_sort	Kelli L. VanDussen
title	Neonatal Mouse Gut Metabolites Influence <named-content content-type="genus-species">Cryptosporidium parvum</named-content> Infection in Intestinal Epithelial Cells
title_short	Neonatal Mouse Gut Metabolites Influence <named-content content-type="genus-species">Cryptosporidium parvum</named-content> Infection in Intestinal Epithelial Cells
title_full	Neonatal Mouse Gut Metabolites Influence <named-content content-type="genus-species">Cryptosporidium parvum</named-content> Infection in Intestinal Epithelial Cells
title_fullStr	Neonatal Mouse Gut Metabolites Influence <named-content content-type="genus-species">Cryptosporidium parvum</named-content> Infection in Intestinal Epithelial Cells
title_full_unstemmed	Neonatal Mouse Gut Metabolites Influence <named-content content-type="genus-species">Cryptosporidium parvum</named-content> Infection in Intestinal Epithelial Cells
title_sort	neonatal mouse gut metabolites influence <named-content content-type="genus-species">cryptosporidium parvum</named-content> infection in intestinal epithelial cells
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/15ba3df73dfa42048c217995bef69455
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Neonatal Mouse Gut Metabolites Influence <named-content content-type="genus-species">Cryptosporidium parvum</named-content> Infection in Intestinal Epithelial Cells

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