Methylglyoxal resistance in Bacillus subtilis: contributions of bacillithiol-dependent and independent pathways

Pete Chandrangsu1, Renata Dusi, Chris J Hamilton

  • 1Department of Microbiology, Cornell University, Ithaca, NY, 14853-8101, USA.

Molecular Microbiology
|December 17, 2013
PubMed

Insights

Bacillus subtilis uses bacillithiol (BSH) to detoxify toxic methylglyoxal (MG) via glyoxalase enzymes, a process crucial for cell survival. This BSH-dependent pathway, involving cytoplasmic acidification, offers protection when glutathione is absent.

Area of Science:

  • Microbiology
  • Biochemistry
  • Cell Biology

Background:

  • Methylglyoxal (MG) is a toxic glycolysis byproduct damaging cellular components.
  • Glutathione typically detoxifies MG, but is absent in Firmicutes like Bacillus subtilis.
  • Bacillithiol (BSH) is identified as a major low-molecular-weight thiol in Firmicutes.

Purpose of the Study:

  • Investigate the role of BSH in methylglyoxal (MG) detoxification in Bacillus subtilis.
  • Identify MG resistance pathways in the absence of glutathione.
  • Elucidate the mechanisms of BSH-dependent and BSH-independent MG resistance.

Main Methods:

  • Cellular depletion of BSH by MG exposure.
  • Enzymatic assays for glyoxalase activity (GlxA, GlxB).
  • Measurement of intracellular pH and K+ efflux.
  • Genetic analysis of MG resistance pathways.

Main Results:

  • MG rapidly depletes BSH in Bacillus subtilis cells.
  • A BSH-dependent pathway using glyoxalase I (GlxA) and glyoxalase II (GlxB) converts MG to d-lactate.
  • The S-lactoyl-BSH intermediate activates the KhtSTU K+ efflux pump, causing protective cytoplasmic acidification.
  • Two BSH-independent pathways involving YdeA/YraA/YfkM (glyoxalase III homologues) and YhdN (aldo-keto reductase) also detoxify MG.

Conclusions:

  • Bacillithiol (BSH) is essential for methylglyoxal (MG) detoxification in Firmicutes.
  • Cytoplasmic acidification, mediated by BSH and K+ efflux, is critical for MG resistance.
  • Bacillus subtilis employs multiple, distinct pathways for MG detoxification, including BSH-dependent and BSH-independent mechanisms.

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