Expanded Glucose Import Capability Affords <named-content content-type="genus-species">Staphylococcus aureus</named-content> Optimized Glycolytic Flux during Infection

ABSTRACT Acquisition of numerous virulence determinants affords Staphylococcus aureus greater pathogenicity than other skin-colonizing staphylococci in humans. Additionally, the metabolic adaptation of S. aureus to nonrespiratory conditions encountered during infection (e.g., hypoxia, nitric oxide,...

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Autores principales:	Nicholas P. Vitko, Melinda R. Grosser, Dal Khatri, Thurlow R. Lance, Anthony R. Richardson
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2016
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/8848b6bf057f493f9e6cf9fcf0284047
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spelling	oai:doaj.org-article:8848b6bf057f493f9e6cf9fcf02840472021-11-15T15:50:16ZExpanded Glucose Import Capability Affords <named-content content-type="genus-species">Staphylococcus aureus</named-content> Optimized Glycolytic Flux during Infection10.1128/mBio.00296-162150-7511https://doaj.org/article/8848b6bf057f493f9e6cf9fcf02840472016-07-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00296-16https://doaj.org/toc/2150-7511ABSTRACT Acquisition of numerous virulence determinants affords Staphylococcus aureus greater pathogenicity than other skin-colonizing staphylococci in humans. Additionally, the metabolic adaptation of S. aureus to nonrespiratory conditions encountered during infection (e.g., hypoxia, nitric oxide, iron chelation) has been implicated as contributing to S. aureus virulence. Specifically, S. aureus has been shown to ferment glycolytic substrates in nonrespiratory environments encountered within the host. Here, we show that S. aureus has acquired unique carbohydrate transporters that facilitate the maximal uptake of host sugars and serve to support nonrespiratory growth in inflamed tissue. The carbohydrate substrates of 11 S. aureus transporters were identified, and at least four of their genes encode S. aureus glucose transporters (glcA, glcB, glcC, and glcU). Moreover, two transporter genes (glcA and glcC) are unique to S. aureus and contribute disproportionately to the nonrespiratory growth of S. aureus on glucose. Targeted inactivation of sugar transporters reduced glucose uptake and attenuated S. aureus in a murine model of skin and soft tissue infections. These data expand the evidence for metabolic adaptation of S. aureus to invasive infection and demonstrate the specific requirement for the fermentation of glucose over all other available carbohydrates. Ultimately, acquisition of foreign genes allows S. aureus to adopt a metabolic strategy resembling that of infiltrating host immune cells: high glycolytic flux coupled to lactate excretion. IMPORTANCE The bacterial pathogen Staphylococcus aureus causes a wide range of human infections that are costly and difficult to treat. S. aureus differs from closely related commensal staphylococci in its ability to flourish following the invasion of deeper tissue from the skin surface. There, S. aureus primarily uses glucose to grow under respiration-limiting conditions imposed by the immune system. It was previously unclear how S. aureus thrives in this environment when other Staphylococcus species cannot. Our results provide evidence that S. aureus has acquired an expanded repertoire of carbohydrate transporters. In particular, four glucose transporters contribute to efficient S. aureus growth during infection. Thus, S. aureus has evolved to maximize its glucose uptake abilities for enhanced glycolytic flux during tissue invasion. This dependence on glucose acquisition for S. aureus virulence may also explain links between serious infectious complications associated with diabetic patients exhibiting elevated blood glucose levels.Nicholas P. VitkoMelinda R. GrosserDal KhatriThurlow R. LanceAnthony R. RichardsonAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 7, Iss 3 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Nicholas P. Vitko Melinda R. Grosser Dal Khatri Thurlow R. Lance Anthony R. Richardson Expanded Glucose Import Capability Affords <named-content content-type="genus-species">Staphylococcus aureus</named-content> Optimized Glycolytic Flux during Infection
description	ABSTRACT Acquisition of numerous virulence determinants affords Staphylococcus aureus greater pathogenicity than other skin-colonizing staphylococci in humans. Additionally, the metabolic adaptation of S. aureus to nonrespiratory conditions encountered during infection (e.g., hypoxia, nitric oxide, iron chelation) has been implicated as contributing to S. aureus virulence. Specifically, S. aureus has been shown to ferment glycolytic substrates in nonrespiratory environments encountered within the host. Here, we show that S. aureus has acquired unique carbohydrate transporters that facilitate the maximal uptake of host sugars and serve to support nonrespiratory growth in inflamed tissue. The carbohydrate substrates of 11 S. aureus transporters were identified, and at least four of their genes encode S. aureus glucose transporters (glcA, glcB, glcC, and glcU). Moreover, two transporter genes (glcA and glcC) are unique to S. aureus and contribute disproportionately to the nonrespiratory growth of S. aureus on glucose. Targeted inactivation of sugar transporters reduced glucose uptake and attenuated S. aureus in a murine model of skin and soft tissue infections. These data expand the evidence for metabolic adaptation of S. aureus to invasive infection and demonstrate the specific requirement for the fermentation of glucose over all other available carbohydrates. Ultimately, acquisition of foreign genes allows S. aureus to adopt a metabolic strategy resembling that of infiltrating host immune cells: high glycolytic flux coupled to lactate excretion. IMPORTANCE The bacterial pathogen Staphylococcus aureus causes a wide range of human infections that are costly and difficult to treat. S. aureus differs from closely related commensal staphylococci in its ability to flourish following the invasion of deeper tissue from the skin surface. There, S. aureus primarily uses glucose to grow under respiration-limiting conditions imposed by the immune system. It was previously unclear how S. aureus thrives in this environment when other Staphylococcus species cannot. Our results provide evidence that S. aureus has acquired an expanded repertoire of carbohydrate transporters. In particular, four glucose transporters contribute to efficient S. aureus growth during infection. Thus, S. aureus has evolved to maximize its glucose uptake abilities for enhanced glycolytic flux during tissue invasion. This dependence on glucose acquisition for S. aureus virulence may also explain links between serious infectious complications associated with diabetic patients exhibiting elevated blood glucose levels.
format	article
author	Nicholas P. Vitko Melinda R. Grosser Dal Khatri Thurlow R. Lance Anthony R. Richardson
author_facet	Nicholas P. Vitko Melinda R. Grosser Dal Khatri Thurlow R. Lance Anthony R. Richardson
author_sort	Nicholas P. Vitko
title	Expanded Glucose Import Capability Affords <named-content content-type="genus-species">Staphylococcus aureus</named-content> Optimized Glycolytic Flux during Infection
title_short	Expanded Glucose Import Capability Affords <named-content content-type="genus-species">Staphylococcus aureus</named-content> Optimized Glycolytic Flux during Infection
title_full	Expanded Glucose Import Capability Affords <named-content content-type="genus-species">Staphylococcus aureus</named-content> Optimized Glycolytic Flux during Infection
title_fullStr	Expanded Glucose Import Capability Affords <named-content content-type="genus-species">Staphylococcus aureus</named-content> Optimized Glycolytic Flux during Infection
title_full_unstemmed	Expanded Glucose Import Capability Affords <named-content content-type="genus-species">Staphylococcus aureus</named-content> Optimized Glycolytic Flux during Infection
title_sort	expanded glucose import capability affords <named-content content-type="genus-species">staphylococcus aureus</named-content> optimized glycolytic flux during infection
publisher	American Society for Microbiology
publishDate	2016
url	https://doaj.org/article/8848b6bf057f493f9e6cf9fcf0284047
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Expanded Glucose Import Capability Affords <named-content content-type="genus-species">Staphylococcus aureus</named-content> Optimized Glycolytic Flux during Infection

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