Protease-Mediated Growth of <named-content content-type="genus-species">Staphylococcus aureus</named-content> on Host Proteins Is <italic toggle="yes">opp3</italic> Dependent

ABSTRACT Staphylococcus aureus has the ability to cause infections in multiple organ systems, suggesting an ability to rapidly adapt to changing carbon and nitrogen sources. Although there is little information about the nutrients available at specific sites of infection, a mature skin abscess has b...

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Autores principales:	McKenzie K. Lehman, Austin S. Nuxoll, Kelsey J. Yamada, Tammy Kielian, Steven D. Carson, Paul D. Fey
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	Staphylococcus aureus amino acid catabolism metabolism proteases Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/5ffaa02fcfd0439e9fedfded29dfb694
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spelling	oai:doaj.org-article:5ffaa02fcfd0439e9fedfded29dfb6942021-11-15T15:55:25ZProtease-Mediated Growth of <named-content content-type="genus-species">Staphylococcus aureus</named-content> on Host Proteins Is <italic toggle="yes">opp3</italic> Dependent10.1128/mBio.02553-182150-7511https://doaj.org/article/5ffaa02fcfd0439e9fedfded29dfb6942019-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02553-18https://doaj.org/toc/2150-7511ABSTRACT Staphylococcus aureus has the ability to cause infections in multiple organ systems, suggesting an ability to rapidly adapt to changing carbon and nitrogen sources. Although there is little information about the nutrients available at specific sites of infection, a mature skin abscess has been characterized as glucose depleted, indicating that peptides and free amino acids are an important source of nutrients for the bacteria. Our studies have found that mutations in enzymes necessary for growth on amino acids, including pyruvate carboxykinase (ΔpckA) and glutamate dehydrogenase (ΔgudB), reduced the ability of the bacteria to proliferate within a skin abscess, suggesting that peptides and free amino acids are important for S. aureus growth. Furthermore, we found that collagen, an abundant host protein that is present throughout a skin abscess, serves as a reservoir of peptides. To liberate peptides from the collagen, we identified that the host protease, MMP-9, as well as the staphylococcal proteases aureolysin and staphopain B function to cleave collagen into peptide fragments that can support S. aureus growth under nutrient-limited conditions. Moreover, the oligopeptide transporter Opp3 is the primary staphylococcal transporter responsible for peptide acquisition. Lastly, we observed that the presence of peptides (3-mer to 7-mer) induces the expression of aureolysin, suggesting that S. aureus has the ability to detect peptides in the environment. IMPORTANCE Staphylococcus aureus has the ability to cause infections in a variety of niches, suggesting a robust metabolic capacity facilitating proliferation under various nutrient conditions. The mature skin abscess is glucose depleted, indicating that peptides and free amino acids are important sources of nutrients for S. aureus. Our studies have found that mutations in both pyruvate carboxykinase and glutamate dehydrogenase, enzymes that function in essential gluconeogenesis reactions when amino acids serve as the major carbon source, reduce bacterial burden in a murine skin abscess model. Moreover, peptides liberated from collagen by host protease MMP-9 as well as the staphylococcal protease aureolysin support S. aureus growth in an Opp3-dependent manner under nutrient-limited conditions. Additionally, the presence of peptides induces aureolysin expression. Overall, these studies define one pathway by which S. aureus senses a nutrient-limiting environment and induces factors that function to acquire and utilize carbon from host-derived sources.McKenzie K. LehmanAustin S. NuxollKelsey J. YamadaTammy KielianSteven D. CarsonPaul D. FeyAmerican Society for MicrobiologyarticleStaphylococcus aureusamino acid catabolismmetabolismproteasesMicrobiologyQR1-502ENmBio, Vol 10, Iss 2 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Staphylococcus aureus amino acid catabolism metabolism proteases Microbiology QR1-502
spellingShingle	Staphylococcus aureus amino acid catabolism metabolism proteases Microbiology QR1-502 McKenzie K. Lehman Austin S. Nuxoll Kelsey J. Yamada Tammy Kielian Steven D. Carson Paul D. Fey Protease-Mediated Growth of <named-content content-type="genus-species">Staphylococcus aureus</named-content> on Host Proteins Is <italic toggle="yes">opp3</italic> Dependent
description	ABSTRACT Staphylococcus aureus has the ability to cause infections in multiple organ systems, suggesting an ability to rapidly adapt to changing carbon and nitrogen sources. Although there is little information about the nutrients available at specific sites of infection, a mature skin abscess has been characterized as glucose depleted, indicating that peptides and free amino acids are an important source of nutrients for the bacteria. Our studies have found that mutations in enzymes necessary for growth on amino acids, including pyruvate carboxykinase (ΔpckA) and glutamate dehydrogenase (ΔgudB), reduced the ability of the bacteria to proliferate within a skin abscess, suggesting that peptides and free amino acids are important for S. aureus growth. Furthermore, we found that collagen, an abundant host protein that is present throughout a skin abscess, serves as a reservoir of peptides. To liberate peptides from the collagen, we identified that the host protease, MMP-9, as well as the staphylococcal proteases aureolysin and staphopain B function to cleave collagen into peptide fragments that can support S. aureus growth under nutrient-limited conditions. Moreover, the oligopeptide transporter Opp3 is the primary staphylococcal transporter responsible for peptide acquisition. Lastly, we observed that the presence of peptides (3-mer to 7-mer) induces the expression of aureolysin, suggesting that S. aureus has the ability to detect peptides in the environment. IMPORTANCE Staphylococcus aureus has the ability to cause infections in a variety of niches, suggesting a robust metabolic capacity facilitating proliferation under various nutrient conditions. The mature skin abscess is glucose depleted, indicating that peptides and free amino acids are important sources of nutrients for S. aureus. Our studies have found that mutations in both pyruvate carboxykinase and glutamate dehydrogenase, enzymes that function in essential gluconeogenesis reactions when amino acids serve as the major carbon source, reduce bacterial burden in a murine skin abscess model. Moreover, peptides liberated from collagen by host protease MMP-9 as well as the staphylococcal protease aureolysin support S. aureus growth in an Opp3-dependent manner under nutrient-limited conditions. Additionally, the presence of peptides induces aureolysin expression. Overall, these studies define one pathway by which S. aureus senses a nutrient-limiting environment and induces factors that function to acquire and utilize carbon from host-derived sources.
format	article
author	McKenzie K. Lehman Austin S. Nuxoll Kelsey J. Yamada Tammy Kielian Steven D. Carson Paul D. Fey
author_facet	McKenzie K. Lehman Austin S. Nuxoll Kelsey J. Yamada Tammy Kielian Steven D. Carson Paul D. Fey
author_sort	McKenzie K. Lehman
title	Protease-Mediated Growth of <named-content content-type="genus-species">Staphylococcus aureus</named-content> on Host Proteins Is <italic toggle="yes">opp3</italic> Dependent
title_short	Protease-Mediated Growth of <named-content content-type="genus-species">Staphylococcus aureus</named-content> on Host Proteins Is <italic toggle="yes">opp3</italic> Dependent
title_full	Protease-Mediated Growth of <named-content content-type="genus-species">Staphylococcus aureus</named-content> on Host Proteins Is <italic toggle="yes">opp3</italic> Dependent
title_fullStr	Protease-Mediated Growth of <named-content content-type="genus-species">Staphylococcus aureus</named-content> on Host Proteins Is <italic toggle="yes">opp3</italic> Dependent
title_full_unstemmed	Protease-Mediated Growth of <named-content content-type="genus-species">Staphylococcus aureus</named-content> on Host Proteins Is <italic toggle="yes">opp3</italic> Dependent
title_sort	protease-mediated growth of <named-content content-type="genus-species">staphylococcus aureus</named-content> on host proteins is <italic toggle="yes">opp3</italic> dependent
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/5ffaa02fcfd0439e9fedfded29dfb694
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Protease-Mediated Growth of <named-content content-type="genus-species">Staphylococcus aureus</named-content> on Host Proteins Is <italic toggle="yes">opp3</italic> Dependent

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