Guanine limitation results in CodY-dependent and -independent alteration of Staphylococcus aureus physiology and gene expression

Alyssa N. King, Samiksha A. Borkar, David J. Samuels, Zachary Batz, Logan L. Bulock, Marat R. Sadykov, Kenneth W Bayles, Shaun R. Brinsmade

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

In Staphylococcus aureus, the global transcriptional regulator CodY modulates the expression of hundreds of genes in response to the availability of GTP and the branched-chain amino acids isoleucine, leucine, and valine (ILV). CodY DNAbinding activity is high when GTP and ILV are abundant. When GTP and ILV are limited, CodY's affinity for DNA drops, altering expression of CodY-regulated targets. In this work, we investigated the impact of guanine nucleotides (GNs) on S. aureus physiology and CodY activity by constructing a guaA null mutant (ΔguaA strain). De novo biosynthesis of guanine monophosphate is abolished due to the guaA mutation; thus, the mutant cells require exogenous guanosine for growth. We also found that CodY activity was reduced when we knocked out guaA, activating the Agr twocomponent system and increasing secreted protease activity. Notably, in a rich, complex medium, we detected an increase in alternative sigma factor B activity in the ΔguaA mutant, which results in a 5-fold increase in production of the antioxidant pigment staphyloxanthin. Under biologically relevant flow conditions, ΔguaA cells failed to form robust biofilms when limited for guanine or guanosine. Transcriptome sequencing (RNA-Seq) analysis of the S. aureus transcriptome during growth in guanosine-limited chemostats revealed substantial CodY-dependent and -independent alterations of gene expression profiles. Importantly, these changes increase production of proteases and δ-toxin, suggesting that S. aureus exhibits a more invasive lifestyle when limited for guanosine. Further, gene products upregulated under GN limitation, including those necessary for lipoic acid biosynthesis and sugar transport, may prove to be useful drug targets for treating Gram-positive infections.

Original languageEnglish (US)
Article numbere00136-18
JournalJournal of bacteriology
Volume200
Issue number14
DOIs
StatePublished - Jul 1 2018

Fingerprint

Guanosine
Guanine
Staphylococcus aureus
Isoleucine
Valine
Guanosine Triphosphate
Transcriptome
Leucine
Gene Expression
Guanine Nucleotides
Peptide Hydrolases
RNA Sequence Analysis
Sigma Factor
Thioctic Acid
Branched Chain Amino Acids
Biofilms
Growth
Life Style
Antioxidants
Mutation

Keywords

  • Agr
  • Biofilms
  • GTP
  • Proteases
  • SigB

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

Cite this

King, A. N., Borkar, S. A., Samuels, D. J., Batz, Z., Bulock, L. L., Sadykov, M. R., ... Brinsmade, S. R. (2018). Guanine limitation results in CodY-dependent and -independent alteration of Staphylococcus aureus physiology and gene expression. Journal of bacteriology, 200(14), [e00136-18]. https://doi.org/10.1128/JB.00136-18

Guanine limitation results in CodY-dependent and -independent alteration of Staphylococcus aureus physiology and gene expression. / King, Alyssa N.; Borkar, Samiksha A.; Samuels, David J.; Batz, Zachary; Bulock, Logan L.; Sadykov, Marat R.; Bayles, Kenneth W; Brinsmade, Shaun R.

In: Journal of bacteriology, Vol. 200, No. 14, e00136-18, 01.07.2018.

Research output: Contribution to journalArticle

King, Alyssa N. ; Borkar, Samiksha A. ; Samuels, David J. ; Batz, Zachary ; Bulock, Logan L. ; Sadykov, Marat R. ; Bayles, Kenneth W ; Brinsmade, Shaun R. / Guanine limitation results in CodY-dependent and -independent alteration of Staphylococcus aureus physiology and gene expression. In: Journal of bacteriology. 2018 ; Vol. 200, No. 14.
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