Aerobic Metabolism in <named-content content-type="genus-species">Vibrio cholerae</named-content> Is Required for Population Expansion during Infection

ABSTRACT Vibrio cholerae replicates to high cell density in the human small intestine, leading to the diarrheal disease cholera. During infection, V. cholerae senses and responds to environmental signals that govern cellular responses. Spatial localization of V. cholerae within the intestine affects...

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Autores principales:	Andrew J. Van Alst, Victor J. DiRita
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	bacterial physiology in vivo fitness PDH PFL mucin metabolism Vibrio cholerae Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/cdea68684aaa4633a7304ca7fc093da1
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spelling	oai:doaj.org-article:cdea68684aaa4633a7304ca7fc093da12021-11-15T16:19:07ZAerobic Metabolism in <named-content content-type="genus-species">Vibrio cholerae</named-content> Is Required for Population Expansion during Infection10.1128/mBio.01989-202150-7511https://doaj.org/article/cdea68684aaa4633a7304ca7fc093da12020-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01989-20https://doaj.org/toc/2150-7511ABSTRACT Vibrio cholerae replicates to high cell density in the human small intestine, leading to the diarrheal disease cholera. During infection, V. cholerae senses and responds to environmental signals that govern cellular responses. Spatial localization of V. cholerae within the intestine affects nutrient availability and metabolic pathways required for replicative success. Metabolic processes used by V. cholerae to reach such high cell densities are not fully known. We sought to better define the metabolic traits that contribute to high levels of V. cholerae during infection. By disrupting the pyruvate dehydrogenase (PDH) complex and pyruvate formate-lyase (PFL), we could differentiate aerobic and anaerobic metabolic pathway involvement in V. cholerae proliferation. We demonstrate that oxidative metabolism is a key contributor to the replicative success of V. cholerae in vivo using an infant mouse model in which PDH mutants were attenuated 100-fold relative to the wild type for colonization. Additionally, metabolism of host substrates, including mucin, was determined to support V. cholerae growth in vitro as a sole carbon source, primarily under aerobic growth conditions. Mucin likely contributes to population expansion during human infection as it is a ubiquitous source of carbohydrates. These data highlight oxidative metabolism as important in the intestinal environment and warrant further investigation of how oxygen and other host substrates shape the intestinal landscape that ultimately influences bacterial disease. We conclude from our results that oxidative metabolism of host substrates is a key driver of V. cholerae proliferation during infection, leading to the substantial bacterial burden exhibited in cholera patients. IMPORTANCE Vibrio cholerae remains a challenge in the developing world and incidence of the disease it causes, cholera, is anticipated to increase with rising global temperatures and with emergent, highly infectious strains. At present, the underlying metabolic processes that support V. cholerae growth during infection are less well understood than specific virulence traits, such as production of a toxin or pilus. In this study, we determined that oxidative metabolism of host substrates such as mucin contribute significantly to V. cholerae population expansion in vivo. Identifying metabolic pathways critical for growth can provide avenues for controlling V. cholerae infection and the knowledge may be translatable to other pathogens of the gastrointestinal tract.Andrew J. Van AlstVictor J. DiRitaAmerican Society for Microbiologyarticlebacterial physiologyin vivo fitnessPDHPFLmucin metabolismVibrio choleraeMicrobiologyQR1-502ENmBio, Vol 11, Iss 5 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	bacterial physiology in vivo fitness PDH PFL mucin metabolism Vibrio cholerae Microbiology QR1-502
spellingShingle	bacterial physiology in vivo fitness PDH PFL mucin metabolism Vibrio cholerae Microbiology QR1-502 Andrew J. Van Alst Victor J. DiRita Aerobic Metabolism in <named-content content-type="genus-species">Vibrio cholerae</named-content> Is Required for Population Expansion during Infection
description	ABSTRACT Vibrio cholerae replicates to high cell density in the human small intestine, leading to the diarrheal disease cholera. During infection, V. cholerae senses and responds to environmental signals that govern cellular responses. Spatial localization of V. cholerae within the intestine affects nutrient availability and metabolic pathways required for replicative success. Metabolic processes used by V. cholerae to reach such high cell densities are not fully known. We sought to better define the metabolic traits that contribute to high levels of V. cholerae during infection. By disrupting the pyruvate dehydrogenase (PDH) complex and pyruvate formate-lyase (PFL), we could differentiate aerobic and anaerobic metabolic pathway involvement in V. cholerae proliferation. We demonstrate that oxidative metabolism is a key contributor to the replicative success of V. cholerae in vivo using an infant mouse model in which PDH mutants were attenuated 100-fold relative to the wild type for colonization. Additionally, metabolism of host substrates, including mucin, was determined to support V. cholerae growth in vitro as a sole carbon source, primarily under aerobic growth conditions. Mucin likely contributes to population expansion during human infection as it is a ubiquitous source of carbohydrates. These data highlight oxidative metabolism as important in the intestinal environment and warrant further investigation of how oxygen and other host substrates shape the intestinal landscape that ultimately influences bacterial disease. We conclude from our results that oxidative metabolism of host substrates is a key driver of V. cholerae proliferation during infection, leading to the substantial bacterial burden exhibited in cholera patients. IMPORTANCE Vibrio cholerae remains a challenge in the developing world and incidence of the disease it causes, cholera, is anticipated to increase with rising global temperatures and with emergent, highly infectious strains. At present, the underlying metabolic processes that support V. cholerae growth during infection are less well understood than specific virulence traits, such as production of a toxin or pilus. In this study, we determined that oxidative metabolism of host substrates such as mucin contribute significantly to V. cholerae population expansion in vivo. Identifying metabolic pathways critical for growth can provide avenues for controlling V. cholerae infection and the knowledge may be translatable to other pathogens of the gastrointestinal tract.
format	article
author	Andrew J. Van Alst Victor J. DiRita
author_facet	Andrew J. Van Alst Victor J. DiRita
author_sort	Andrew J. Van Alst
title	Aerobic Metabolism in <named-content content-type="genus-species">Vibrio cholerae</named-content> Is Required for Population Expansion during Infection
title_short	Aerobic Metabolism in <named-content content-type="genus-species">Vibrio cholerae</named-content> Is Required for Population Expansion during Infection
title_full	Aerobic Metabolism in <named-content content-type="genus-species">Vibrio cholerae</named-content> Is Required for Population Expansion during Infection
title_fullStr	Aerobic Metabolism in <named-content content-type="genus-species">Vibrio cholerae</named-content> Is Required for Population Expansion during Infection
title_full_unstemmed	Aerobic Metabolism in <named-content content-type="genus-species">Vibrio cholerae</named-content> Is Required for Population Expansion during Infection
title_sort	aerobic metabolism in <named-content content-type="genus-species">vibrio cholerae</named-content> is required for population expansion during infection
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/cdea68684aaa4633a7304ca7fc093da1
work_keys_str_mv	AT andrewjvanalst aerobicmetabolisminnamedcontentcontenttypegenusspeciesvibriocholeraenamedcontentisrequiredforpopulationexpansionduringinfection AT victorjdirita aerobicmetabolisminnamedcontentcontenttypegenusspeciesvibriocholeraenamedcontentisrequiredforpopulationexpansionduringinfection
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Aerobic Metabolism in <named-content content-type="genus-species">Vibrio cholerae</named-content> Is Required for Population Expansion during Infection

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