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Association of Metal Homeostasis and (p)ppGpp Regulation in the Pathophysiology of Enterococcus faecalis

C Colomer-Winter1, A O Gaca2, J A Lemos3

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

Infection and Immunity
|May 10, 2017
PubMed

Insights

The (p)ppGpp molecule regulates metal homeostasis in Enterococcus faecalis, impacting its virulence and survival. This finding offers new therapeutic strategies against bacterial infections.

Area of Science:

  • Microbiology
  • Bacterial Pathogenesis
  • Molecular Biology

Background:

  • The regulatory nucleotides, guanosine tetraphosphate (ppGpp) and pentaphosphate (pppGpp), collectively known as (p)ppGpp, are crucial for Enterococcus faecalis virulence.
  • Nutritional immunity restricts essential metals like iron (Fe) and manganese (Mn) for invading pathogens.
  • The precise mechanisms by which (p)ppGpp enhances virulence in E. faecalis remain unclear.

Purpose of the Study:

  • To investigate the role of (p)ppGpp in regulating metal homeostasis in E. faecalis.
  • To determine if (p)ppGpp mediates virulence through iron and manganese regulation.
  • To explore the connection between (p)ppGpp, metal ions, and reactive oxygen species (ROS) resistance.

Main Methods:

  • Generating a ΔrelΔrelQ mutant strain lacking (p)ppGpp production.
  • Supplementing bacterial growth media with iron or manganese.
  • Utilizing chemically defined media to assess growth and (p)ppGpp accumulation under varying metal conditions.
  • Performing transcriptional analysis and physiological investigations.

Main Results:

  • Supplementation with Fe or Mn restored the growth and survival of the (p)ppGpp-deficient strain.
  • (p)ppGpp levels increased in response to Fe or Mn depletion.
  • The (p)ppGpp-deficient strain exhibited a significant growth requirement for Mn, which Fe could alleviate.
  • The (p)ppGpp-deficient strain showed increased sensitivity to reactive oxygen species, requiring higher Mn levels for coping.

Conclusions:

  • (p)ppGpp plays a vital role in managing metal homeostasis in E. faecalis.
  • This regulation is linked to bacterial virulence and survival under host nutritional immunity.
  • Understanding the (p)ppGpp-mediated metal regulation offers potential therapeutic targets against E. faecalis infections.
Keywords:
(p)ppGppEnterococcusmanganesemetal homeostasisnutritional immunityoxidative stress

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