The Staphylococcus aureus α-acetolactate synthase ALS confers resistance to nitrosative stress

Sandra M. Carvalho, Anne de Jong, Tomas G. Kloosterman, Oscar P. Kuipers, Lígia M. Saraiva

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Staphylococcus aureus is a worldwide pathogen that colonizes the human nasal cavity and is a major cause of respiratory and cutaneous infections. In the nasal cavity, S. aureus thrives with high concentrations of nitric oxide (NO) produced by the innate immune effectors and has available for growth slow-metabolizing free hexoses, such as galactose. Here, we have used deep sequencing transcriptomic analysis (RNA-Seq) and 1H-NMR to uncover how S. aureus grown on galactose, a major carbon source present in the nasopharynx, survives the deleterious action of NO. We observed that, like on glucose, S. aureus withstands high concentrations of NO when using galactose. Data indicate that this resistance is, most likely, achieved through a distinct metabolism that relies on the increased production of amino acids, such as glutamate, threonine, and branched-chain amino acids (BCAAs). Moreover, we found that under NO stress the S. aureus α-acetolactate synthase (ALS) enzyme, which converts pyruvate into α-acetolactate, plays an important role. ALS is proposed to prevent intracellular acidification, to promote the production of BCAAs and the activation of the TCA cycle. Additionally, ALS is shown to contribute to the successful infection of murine macrophages. Furthermore, ALS contributes to the resistance of S. aureus to beta-lactam antibiotics such as methicillin and oxacillin.

Original languageEnglish
Article number1273
JournalFrontiers in Microbiology
Volume8
Issue numberJUL
DOIs
Publication statusPublished - 11 Jul 2017

Fingerprint

Acetolactate Synthase
Staphylococcus aureus
Nitric Oxide
Galactose
Branched Chain Amino Acids
Nasal Cavity
High-Throughput Nucleotide Sequencing
Oxacillin
Methicillin
Hexoses
Nasopharynx
beta-Lactams
Threonine
Pyruvic Acid
Respiratory Tract Infections
Glutamic Acid
Carbon
Macrophages
RNA
Anti-Bacterial Agents

Keywords

  • A-acetolactate synthase (ALS)
  • Bacterial metabolism
  • Nitrosative stress
  • Nuclear magnetic resonance (NMR)
  • Staphylococcus aureus

Cite this

Carvalho, Sandra M. ; de Jong, Anne ; Kloosterman, Tomas G. ; Kuipers, Oscar P. ; Saraiva, Lígia M. / The Staphylococcus aureus α-acetolactate synthase ALS confers resistance to nitrosative stress. In: Frontiers in Microbiology. 2017 ; Vol. 8, No. JUL.
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The Staphylococcus aureus α-acetolactate synthase ALS confers resistance to nitrosative stress. / Carvalho, Sandra M.; de Jong, Anne; Kloosterman, Tomas G.; Kuipers, Oscar P.; Saraiva, Lígia M.

In: Frontiers in Microbiology, Vol. 8, No. JUL, 1273, 11.07.2017.

Research output: Contribution to journalArticle

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