Metabolic Modeling of <named-content content-type="genus-species">Streptococcus mutans</named-content> Reveals Complex Nutrient Requirements of an Oral Pathogen

ABSTRACT Streptococcus mutans is a Gram-positive bacterium that thrives under acidic conditions and is a primary cause of tooth decay (dental caries). To better understand the metabolism of S. mutans on a systematic level, we manually constructed a genome-scale metabolic model of the S. mutans type...

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Autores principales:	Kenan Jijakli, Paul A. Jensen
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	Streptococcus mutans dental caries flux balance analysis metabolic modeling Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/7fc2f17d52f24c95a787466888efc854
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spelling	oai:doaj.org-article:7fc2f17d52f24c95a787466888efc8542021-12-02T18:39:15ZMetabolic Modeling of <named-content content-type="genus-species">Streptococcus mutans</named-content> Reveals Complex Nutrient Requirements of an Oral Pathogen10.1128/mSystems.00529-192379-5077https://doaj.org/article/7fc2f17d52f24c95a787466888efc8542019-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSystems.00529-19https://doaj.org/toc/2379-5077ABSTRACT Streptococcus mutans is a Gram-positive bacterium that thrives under acidic conditions and is a primary cause of tooth decay (dental caries). To better understand the metabolism of S. mutans on a systematic level, we manually constructed a genome-scale metabolic model of the S. mutans type strain UA159. The model, called iSMU, contains 675 reactions involving 429 metabolites and the products of 493 genes. We validated iSMU by comparing simulations with growth experiments in defined medium. The model simulations matched experimental results for 17 of 18 carbon source utilization assays and 47 of 49 nutrient depletion assays. We also simulated the effects of single gene deletions. The model’s predictions agreed with 78.1% and 84.4% of the gene essentiality predictions from two experimental data sets. Our manually curated model is more accurate than S. mutans models generated from automated reconstruction pipelines and more complete than other manually curated models. We used iSMU to generate hypotheses about the S. mutans metabolic network. Subsequent genetic experiments confirmed that (i) S. mutans catabolizes sorbitol via a sorbitol-6-phosphate 2-dehydrogenase (SMU_308) and (ii) the Leloir pathway is required for growth on complex carbohydrates such as raffinose. We believe the iSMU model is an important resource for understanding the metabolism of S. mutans and guiding future experiments. IMPORTANCE Tooth decay is the most prevalent chronic disease in the United States. Decay is caused by the bacterium Streptococcus mutans, an oral pathogen that ferments sugars into tooth-destroying lactic acid. We constructed a complete metabolic model of S. mutans to systematically investigate how the bacterium grows. The model provides a valuable resource for understanding and targeting S. mutans’ ability to outcompete other species in the oral microbiome.Kenan JijakliPaul A. JensenAmerican Society for MicrobiologyarticleStreptococcus mutansdental cariesflux balance analysismetabolic modelingMicrobiologyQR1-502ENmSystems, Vol 4, Iss 5 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Streptococcus mutans dental caries flux balance analysis metabolic modeling Microbiology QR1-502
spellingShingle	Streptococcus mutans dental caries flux balance analysis metabolic modeling Microbiology QR1-502 Kenan Jijakli Paul A. Jensen Metabolic Modeling of <named-content content-type="genus-species">Streptococcus mutans</named-content> Reveals Complex Nutrient Requirements of an Oral Pathogen
description	ABSTRACT Streptococcus mutans is a Gram-positive bacterium that thrives under acidic conditions and is a primary cause of tooth decay (dental caries). To better understand the metabolism of S. mutans on a systematic level, we manually constructed a genome-scale metabolic model of the S. mutans type strain UA159. The model, called iSMU, contains 675 reactions involving 429 metabolites and the products of 493 genes. We validated iSMU by comparing simulations with growth experiments in defined medium. The model simulations matched experimental results for 17 of 18 carbon source utilization assays and 47 of 49 nutrient depletion assays. We also simulated the effects of single gene deletions. The model’s predictions agreed with 78.1% and 84.4% of the gene essentiality predictions from two experimental data sets. Our manually curated model is more accurate than S. mutans models generated from automated reconstruction pipelines and more complete than other manually curated models. We used iSMU to generate hypotheses about the S. mutans metabolic network. Subsequent genetic experiments confirmed that (i) S. mutans catabolizes sorbitol via a sorbitol-6-phosphate 2-dehydrogenase (SMU_308) and (ii) the Leloir pathway is required for growth on complex carbohydrates such as raffinose. We believe the iSMU model is an important resource for understanding the metabolism of S. mutans and guiding future experiments. IMPORTANCE Tooth decay is the most prevalent chronic disease in the United States. Decay is caused by the bacterium Streptococcus mutans, an oral pathogen that ferments sugars into tooth-destroying lactic acid. We constructed a complete metabolic model of S. mutans to systematically investigate how the bacterium grows. The model provides a valuable resource for understanding and targeting S. mutans’ ability to outcompete other species in the oral microbiome.
format	article
author	Kenan Jijakli Paul A. Jensen
author_facet	Kenan Jijakli Paul A. Jensen
author_sort	Kenan Jijakli
title	Metabolic Modeling of <named-content content-type="genus-species">Streptococcus mutans</named-content> Reveals Complex Nutrient Requirements of an Oral Pathogen
title_short	Metabolic Modeling of <named-content content-type="genus-species">Streptococcus mutans</named-content> Reveals Complex Nutrient Requirements of an Oral Pathogen
title_full	Metabolic Modeling of <named-content content-type="genus-species">Streptococcus mutans</named-content> Reveals Complex Nutrient Requirements of an Oral Pathogen
title_fullStr	Metabolic Modeling of <named-content content-type="genus-species">Streptococcus mutans</named-content> Reveals Complex Nutrient Requirements of an Oral Pathogen
title_full_unstemmed	Metabolic Modeling of <named-content content-type="genus-species">Streptococcus mutans</named-content> Reveals Complex Nutrient Requirements of an Oral Pathogen
title_sort	metabolic modeling of <named-content content-type="genus-species">streptococcus mutans</named-content> reveals complex nutrient requirements of an oral pathogen
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/7fc2f17d52f24c95a787466888efc854
work_keys_str_mv	AT kenanjijakli metabolicmodelingofnamedcontentcontenttypegenusspeciesstreptococcusmutansnamedcontentrevealscomplexnutrientrequirementsofanoralpathogen AT paulajensen metabolicmodelingofnamedcontentcontenttypegenusspeciesstreptococcusmutansnamedcontentrevealscomplexnutrientrequirementsofanoralpathogen
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Metabolic Modeling of <named-content content-type="genus-species">Streptococcus mutans</named-content> Reveals Complex Nutrient Requirements of an Oral Pathogen

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