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Characterization of Staphylococcus aureus responses to spermine stress

Xiangyu Yao1, Chung-Dar Lu

  • 1Department of Biology, Georgia State University, Atlanta, GA, 30303, USA, xyao11@syr.edu.

Current Microbiology
|May 13, 2014
PubMed

Insights

Spermine (Spm) shows synergistic effects with β-lactams against MRSA. Transcriptome analysis reveals Spm alters iron acquisition, down-regulates the SigB regulon, and affects osmotic balance, contributing to its antibacterial toxicity.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Genomics

Background:

  • Spermine (Spm) is a polyamine with known bactericidal properties.
  • Spm exhibits synergistic effects with β-lactams against methicillin-resistant Staphylococcus aureus (MRSA).
  • Understanding Spm's antibacterial targets is crucial for developing new anti-MRSA strategies.

Purpose of the Study:

  • To investigate the molecular mechanisms and antibacterial targets of Spermine (Spm) in Staphylococcus aureus.
  • To analyze the global gene expression changes induced by Spm exposure in MRSA.

Main Methods:

  • Time course-dependent transcriptome analysis using RNA sequencing.
  • Exposure of MRSA (Mu50 strain) to Spm in the absence and presence of tetracycline.
  • Analysis of gene expression patterns, including those related to iron acquisition, SigB regulon, and osmotic balance.

Main Results:

  • Spm down-regulated genes in the SigB regulon and ATP-producing pathways.
  • Genes involved in iron acquisition were significantly induced by Spm, suggesting an interaction with iron metabolism.
  • The tetM gene (tetracycline resistance) was specifically upregulated by Spm and tetracycline, but this did not confer Spm resistance.
  • Genes related to osmotic balance, such as kdpABCDE, were induced by Spm stress.
  • Addition of KCl or NaCl increased the Spm Minimum Inhibitory Concentration (MIC) over 30-fold.

Conclusions:

  • Spm exposure induces a distinct transcriptional response in MRSA.
  • Spm may exert toxicity by altering intracellular iron status and suppressing the SigB regulon.
  • Spm's effects on osmotic balance and ion transport are significant factors in its antibacterial activity.

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