Amino Acid Catabolism in <italic toggle="yes">Staphylococcus aureus</italic> and the Function of Carbon Catabolite Repression

ABSTRACT Staphylococcus aureus must rapidly adapt to a variety of carbon and nitrogen sources during invasion of a host. Within a staphylococcal abscess, preferred carbon sources such as glucose are limiting, suggesting that S. aureus survives through the catabolism of secondary carbon sources. S. a...

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Autores principales:	Cortney R. Halsey, Shulei Lei, Jacqueline K. Wax, Mckenzie K. Lehman, Austin S. Nuxoll, Laurey Steinke, Marat Sadykov, Robert Powers, Paul D. Fey
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/7e448f943df6474093a5fa3ab2f51302
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spelling	oai:doaj.org-article:7e448f943df6474093a5fa3ab2f513022021-11-15T15:51:06ZAmino Acid Catabolism in <italic toggle="yes">Staphylococcus aureus</italic> and the Function of Carbon Catabolite Repression10.1128/mBio.01434-162150-7511https://doaj.org/article/7e448f943df6474093a5fa3ab2f513022017-03-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01434-16https://doaj.org/toc/2150-7511ABSTRACT Staphylococcus aureus must rapidly adapt to a variety of carbon and nitrogen sources during invasion of a host. Within a staphylococcal abscess, preferred carbon sources such as glucose are limiting, suggesting that S. aureus survives through the catabolism of secondary carbon sources. S. aureus encodes pathways to catabolize multiple amino acids, including those that generate pyruvate, 2-oxoglutarate, and oxaloacetate. To assess amino acid catabolism, S. aureus JE2 and mutants were grown in complete defined medium containing 18 amino acids but lacking glucose (CDM). A mutation in the gudB gene, coding for glutamate dehydrogenase, which generates 2-oxoglutarate from glutamate, significantly reduced growth in CDM, suggesting that glutamate and those amino acids generating glutamate, particularly proline, serve as the major carbon source in this medium. Nuclear magnetic resonance (NMR) studies confirmed this supposition. Furthermore, a mutation in the ackA gene, coding for acetate kinase, also abrogated growth of JE2 in CDM, suggesting that ATP production from pyruvate-producing amino acids is also critical for growth. In addition, although a functional respiratory chain was absolutely required for growth, the oxygen consumption rate and intracellular ATP concentration were significantly lower during growth in CDM than during growth in glucose-containing media. Finally, transcriptional analyses demonstrated that expression levels of genes coding for the enzymes that synthesize glutamate from proline, arginine, and histidine are repressed by CcpA and carbon catabolite repression. These data show that pathways important for glutamate catabolism or ATP generation via Pta/AckA are important for growth in niches where glucose is not abundant, such as abscesses within skin and soft tissue infections. IMPORTANCE S. aureus is a significant cause of both morbidity and mortality worldwide. This bacterium causes infections in a wide variety of organ systems, the most common being skin and soft tissue. Within a staphylococcal abscess, levels of glucose, a preferred carbon source, are limited due to the host immune response. Therefore, S. aureus must utilize other available carbon sources such as amino acids or peptides to proliferate. Our results show that glutamate and amino acids that serve as substrates for glutamate synthesis, particularly proline, function as major carbon sources during growth, whereas other amino acids that generate pyruvate are important for ATP synthesis via substrate-level phosphorylation in the Pta-AckA pathway. Our data support a model whereby certain amino acid catabolic pathways, and acquisition of those particular amino acids, are crucial for growth in niches where glucose is not abundant.Cortney R. HalseyShulei LeiJacqueline K. WaxMckenzie K. LehmanAustin S. NuxollLaurey SteinkeMarat SadykovRobert PowersPaul D. FeyAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 8, Iss 1 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Cortney R. Halsey Shulei Lei Jacqueline K. Wax Mckenzie K. Lehman Austin S. Nuxoll Laurey Steinke Marat Sadykov Robert Powers Paul D. Fey Amino Acid Catabolism in <italic toggle="yes">Staphylococcus aureus</italic> and the Function of Carbon Catabolite Repression
description	ABSTRACT Staphylococcus aureus must rapidly adapt to a variety of carbon and nitrogen sources during invasion of a host. Within a staphylococcal abscess, preferred carbon sources such as glucose are limiting, suggesting that S. aureus survives through the catabolism of secondary carbon sources. S. aureus encodes pathways to catabolize multiple amino acids, including those that generate pyruvate, 2-oxoglutarate, and oxaloacetate. To assess amino acid catabolism, S. aureus JE2 and mutants were grown in complete defined medium containing 18 amino acids but lacking glucose (CDM). A mutation in the gudB gene, coding for glutamate dehydrogenase, which generates 2-oxoglutarate from glutamate, significantly reduced growth in CDM, suggesting that glutamate and those amino acids generating glutamate, particularly proline, serve as the major carbon source in this medium. Nuclear magnetic resonance (NMR) studies confirmed this supposition. Furthermore, a mutation in the ackA gene, coding for acetate kinase, also abrogated growth of JE2 in CDM, suggesting that ATP production from pyruvate-producing amino acids is also critical for growth. In addition, although a functional respiratory chain was absolutely required for growth, the oxygen consumption rate and intracellular ATP concentration were significantly lower during growth in CDM than during growth in glucose-containing media. Finally, transcriptional analyses demonstrated that expression levels of genes coding for the enzymes that synthesize glutamate from proline, arginine, and histidine are repressed by CcpA and carbon catabolite repression. These data show that pathways important for glutamate catabolism or ATP generation via Pta/AckA are important for growth in niches where glucose is not abundant, such as abscesses within skin and soft tissue infections. IMPORTANCE S. aureus is a significant cause of both morbidity and mortality worldwide. This bacterium causes infections in a wide variety of organ systems, the most common being skin and soft tissue. Within a staphylococcal abscess, levels of glucose, a preferred carbon source, are limited due to the host immune response. Therefore, S. aureus must utilize other available carbon sources such as amino acids or peptides to proliferate. Our results show that glutamate and amino acids that serve as substrates for glutamate synthesis, particularly proline, function as major carbon sources during growth, whereas other amino acids that generate pyruvate are important for ATP synthesis via substrate-level phosphorylation in the Pta-AckA pathway. Our data support a model whereby certain amino acid catabolic pathways, and acquisition of those particular amino acids, are crucial for growth in niches where glucose is not abundant.
format	article
author	Cortney R. Halsey Shulei Lei Jacqueline K. Wax Mckenzie K. Lehman Austin S. Nuxoll Laurey Steinke Marat Sadykov Robert Powers Paul D. Fey
author_facet	Cortney R. Halsey Shulei Lei Jacqueline K. Wax Mckenzie K. Lehman Austin S. Nuxoll Laurey Steinke Marat Sadykov Robert Powers Paul D. Fey
author_sort	Cortney R. Halsey
title	Amino Acid Catabolism in <italic toggle="yes">Staphylococcus aureus</italic> and the Function of Carbon Catabolite Repression
title_short	Amino Acid Catabolism in <italic toggle="yes">Staphylococcus aureus</italic> and the Function of Carbon Catabolite Repression
title_full	Amino Acid Catabolism in <italic toggle="yes">Staphylococcus aureus</italic> and the Function of Carbon Catabolite Repression
title_fullStr	Amino Acid Catabolism in <italic toggle="yes">Staphylococcus aureus</italic> and the Function of Carbon Catabolite Repression
title_full_unstemmed	Amino Acid Catabolism in <italic toggle="yes">Staphylococcus aureus</italic> and the Function of Carbon Catabolite Repression
title_sort	amino acid catabolism in <italic toggle="yes">staphylococcus aureus</italic> and the function of carbon catabolite repression
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/7e448f943df6474093a5fa3ab2f51302
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Amino Acid Catabolism in <italic toggle="yes">Staphylococcus aureus</italic> and the Function of Carbon Catabolite Repression

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