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Regulatory circuits controlling Spx levels in Streptococcus mutans.

Tridib Ganguly1, Jessica K Kajfasz1, Jacqueline Abranches1

  • 1Department of Oral Biology, College of Dentistry, University of Florida, Gainesville, FL, USA.

Molecular Microbiology
|March 20, 2020
PubMed
Summary

Streptococcus mutans utilizes two Spx proteins, SpxA1 and SpxA2, to manage stress. Their distinct C-terminal regions and regulatory pathways, involving proteases and specific stress regulators, dictate their roles in oxidative and envelope stress responses.

Keywords:
Streptococcus mutansClpPSpxoxidative stress

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Area of Science:

  • Microbiology
  • Molecular Biology
  • Biochemistry

Background:

  • Spx proteins are key regulators of stress responses in Firmicutes.
  • Two Spx homologues, SpxA1 and SpxA2, mediate oxidative stress in Streptococcus mutans.
  • The regulatory mechanisms governing SpxA1 and SpxA2 levels and activity are largely unknown.

Purpose of the Study:

  • To elucidate the regulatory circuits controlling SpxA1 and SpxA2 levels and activity in S. mutans.
  • To investigate the role of C-terminal protein sequences in Spx stability and function.
  • To determine the specific stress responses mediated by SpxA1 and SpxA2.

Main Methods:

  • Green fluorescence protein (GFP) reporter fusions to analyze protein stability.
  • Analysis of protein stability in various protease mutants (clpP, clpC, clpE).
  • Promoter reporter fusions to study transcriptional regulation.
  • Assessment of S. mutans growth under different stress conditions.

Main Results:

  • The C-terminal acidic tail of SpxA1 confers stability, while the SpxA2 C-terminus is unstable and targeted by Clp proteases.
  • Acidic amino acid additions stabilize SpxA2, and deletions destabilize SpxA1.
  • spxA1 transcription is repressed by PerR and SloR; spxA2 transcription depends on the LiaFSR envelope stress system.
  • SpxA2 is crucial for growth under envelope stress, while SpxA1 requires redox sensing for oxidative stress response activation.

Conclusions:

  • SpxA1 and SpxA2 stability and function are differentially regulated by their C-terminal sequences and specific proteases.
  • Distinct transcriptional regulatory pathways govern spxA1 and spxA2 expression, linking them to different stress responses.
  • SpxA1 is primarily involved in oxidative stress, dependent on redox sensing, while SpxA2 mediates envelope stress responses.