Infection Susceptibility in Gastric Intrinsic Factor (Vitamin B<sub>12</sub>)-Defective Mice Is Subject to Maternal Influences

ABSTRACT Mice harboring a mutation in the gene encoding gastric intrinsic factor (Gif), a protein essential for the absorption of vitamin B12/cobalamin (Cbl), have potential as a model to explore the role of vitamins in infection. The levels of Cbl in the blood of Giftm1a/tm1a mutant mice were influ...

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Autores principales:	Lynda Mottram, Anneliese O. Speak, Reza M. Selek, Emma L. Cambridge, Zoe McIntyre, Leanne Kane, Subhankar Mukhopadhyay, Carolyn Grove, Amy Colin, Cordelia Brandt, Maria A. Duque-Correa, Jessica Forbester, Tu Anh Pham Nguyen, Christine Hale, George S. Vasilliou, Mark J. Arends, Brendan W. Wren, Gordon Dougan, Simon Clare
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2016
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/82528246208e4de2981928bb9b56c77c
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spelling	oai:doaj.org-article:82528246208e4de2981928bb9b56c77c2021-11-15T15:50:15ZInfection Susceptibility in Gastric Intrinsic Factor (Vitamin B<sub>12</sub>)-Defective Mice Is Subject to Maternal Influences10.1128/mBio.00830-162150-7511https://doaj.org/article/82528246208e4de2981928bb9b56c77c2016-07-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00830-16https://doaj.org/toc/2150-7511ABSTRACT Mice harboring a mutation in the gene encoding gastric intrinsic factor (Gif), a protein essential for the absorption of vitamin B12/cobalamin (Cbl), have potential as a model to explore the role of vitamins in infection. The levels of Cbl in the blood of Giftm1a/tm1a mutant mice were influenced by the maternal genotype, with offspring born to heterozygous (high Cbl, F1) mothers exhibiting a significantly higher serum Cbl level than those born to homozygous (low Cbl, F2) equivalents. Low Cbl levels correlated with susceptibility to an infectious challenge with Salmonella enterica serovar Typhimurium or Citrobacter rodentium, and this susceptibility phenotype was moderated by Cbl administration. Transcriptional and metabolic profiling revealed that Cbl deficient mice exhibited a bioenergetic shift similar to a metabolic phenomenon commonly found in cancerous cells under hypoxic conditions known as the Warburg effect, with this metabolic effect being exacerbated further by infection. Our findings demonstrate a role for Cbl in bacterial infection, with potential general relevance to dietary deficiency and infection susceptibility. IMPORTANCE Malnutrition continues to be a major public health problem in countries with weak infrastructures. In communities with a high prevalence of poor diet, malnourishment and infectious disease can impact vulnerable individuals such as pregnant women and children. Here, we describe a highly flexible murine model for monitoring maternal and environmental influences of vitamin B12 metabolism. We also demonstrate the potential importance of vitamin B12 in controlling susceptibility to bacterial pathogens such as C. rodentium and S. Typhimurium. We postulate that this model, along with similarly vitamin deficient mice, could be used to further explore the mechanisms associated with micronutrients and susceptibility to diseases, thereby increasing our understanding of disease in the malnourished.Lynda MottramAnneliese O. SpeakReza M. SelekEmma L. CambridgeZoe McIntyreLeanne KaneSubhankar MukhopadhyayCarolyn GroveAmy ColinCordelia BrandtMaria A. Duque-CorreaJessica ForbesterTu Anh Pham NguyenChristine HaleGeorge S. VasilliouMark J. ArendsBrendan W. WrenGordon DouganSimon ClareAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 7, Iss 3 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Lynda Mottram Anneliese O. Speak Reza M. Selek Emma L. Cambridge Zoe McIntyre Leanne Kane Subhankar Mukhopadhyay Carolyn Grove Amy Colin Cordelia Brandt Maria A. Duque-Correa Jessica Forbester Tu Anh Pham Nguyen Christine Hale George S. Vasilliou Mark J. Arends Brendan W. Wren Gordon Dougan Simon Clare Infection Susceptibility in Gastric Intrinsic Factor (Vitamin B<sub>12</sub>)-Defective Mice Is Subject to Maternal Influences
description	ABSTRACT Mice harboring a mutation in the gene encoding gastric intrinsic factor (Gif), a protein essential for the absorption of vitamin B12/cobalamin (Cbl), have potential as a model to explore the role of vitamins in infection. The levels of Cbl in the blood of Giftm1a/tm1a mutant mice were influenced by the maternal genotype, with offspring born to heterozygous (high Cbl, F1) mothers exhibiting a significantly higher serum Cbl level than those born to homozygous (low Cbl, F2) equivalents. Low Cbl levels correlated with susceptibility to an infectious challenge with Salmonella enterica serovar Typhimurium or Citrobacter rodentium, and this susceptibility phenotype was moderated by Cbl administration. Transcriptional and metabolic profiling revealed that Cbl deficient mice exhibited a bioenergetic shift similar to a metabolic phenomenon commonly found in cancerous cells under hypoxic conditions known as the Warburg effect, with this metabolic effect being exacerbated further by infection. Our findings demonstrate a role for Cbl in bacterial infection, with potential general relevance to dietary deficiency and infection susceptibility. IMPORTANCE Malnutrition continues to be a major public health problem in countries with weak infrastructures. In communities with a high prevalence of poor diet, malnourishment and infectious disease can impact vulnerable individuals such as pregnant women and children. Here, we describe a highly flexible murine model for monitoring maternal and environmental influences of vitamin B12 metabolism. We also demonstrate the potential importance of vitamin B12 in controlling susceptibility to bacterial pathogens such as C. rodentium and S. Typhimurium. We postulate that this model, along with similarly vitamin deficient mice, could be used to further explore the mechanisms associated with micronutrients and susceptibility to diseases, thereby increasing our understanding of disease in the malnourished.
format	article
author	Lynda Mottram Anneliese O. Speak Reza M. Selek Emma L. Cambridge Zoe McIntyre Leanne Kane Subhankar Mukhopadhyay Carolyn Grove Amy Colin Cordelia Brandt Maria A. Duque-Correa Jessica Forbester Tu Anh Pham Nguyen Christine Hale George S. Vasilliou Mark J. Arends Brendan W. Wren Gordon Dougan Simon Clare
author_facet	Lynda Mottram Anneliese O. Speak Reza M. Selek Emma L. Cambridge Zoe McIntyre Leanne Kane Subhankar Mukhopadhyay Carolyn Grove Amy Colin Cordelia Brandt Maria A. Duque-Correa Jessica Forbester Tu Anh Pham Nguyen Christine Hale George S. Vasilliou Mark J. Arends Brendan W. Wren Gordon Dougan Simon Clare
author_sort	Lynda Mottram
title	Infection Susceptibility in Gastric Intrinsic Factor (Vitamin B<sub>12</sub>)-Defective Mice Is Subject to Maternal Influences
title_short	Infection Susceptibility in Gastric Intrinsic Factor (Vitamin B<sub>12</sub>)-Defective Mice Is Subject to Maternal Influences
title_full	Infection Susceptibility in Gastric Intrinsic Factor (Vitamin B<sub>12</sub>)-Defective Mice Is Subject to Maternal Influences
title_fullStr	Infection Susceptibility in Gastric Intrinsic Factor (Vitamin B<sub>12</sub>)-Defective Mice Is Subject to Maternal Influences
title_full_unstemmed	Infection Susceptibility in Gastric Intrinsic Factor (Vitamin B<sub>12</sub>)-Defective Mice Is Subject to Maternal Influences
title_sort	infection susceptibility in gastric intrinsic factor (vitamin b<sub>12</sub>)-defective mice is subject to maternal influences
publisher	American Society for Microbiology
publishDate	2016
url	https://doaj.org/article/82528246208e4de2981928bb9b56c77c
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Infection Susceptibility in Gastric Intrinsic Factor (Vitamin B<sub>12</sub>)-Defective Mice Is Subject to Maternal Influences

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