Small proteins regulate Salmonella survival inside macrophages by controlling degradation of a magnesium transporter

Jinki Yeom1,2,3, Yi Shao1, Eduardo A Groisman4,5

  • 1Department of Microbial Pathogenesis, Yale School of Medicine, New Haven, CT 06536.

Insights

Salmonella uses small proteins to control magnesium transporter MgtB levels. MgtR promotes MgtB degradation, while MgtU prevents it, ensuring pathogen survival in macrophages.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Host-Pathogen Interactions

Background:

  • Magnesium (Mg2+) is essential for cell replication and proliferation.
  • The macrophage protein Slc11a1 limits microbial invasion by inducing Mg2+ starvation.
  • Salmonella enterica serovar Typhimurium utilizes the Mg2+ transporter MgtB to cause disease in mice with functional Slc11a1.

Purpose of the Study:

  • To investigate how Salmonella preserves MgtB for survival within macrophages.
  • To identify the regulatory mechanisms controlling MgtB abundance in Salmonella.

Main Methods:

  • Investigated the roles of small proteins MgtR and MgtU in regulating MgtB stability.
  • Utilized genetic manipulation and proteolysis assays.
  • Examined MgtB and MgtA transporter regulation.

Main Results:

  • Salmonella small protein MgtR promotes MgtB degradation via the FtsH protease.
  • Small protein MgtU prevents MgtB proteolysis, even in the absence of MgtR.
  • MgtU is crucial for Salmonella survival in Slc11a1+/+ macrophages, oxidative stress resistance, and growth under Mg2+ limitation.
  • MgtU does not protect the related MgtA transporter from degradation.

Conclusions:

  • Small proteins MgtR and MgtU dynamically regulate the abundance of the MgtB Mg2+ transporter.
  • This regulation is critical for Salmonella survival within host macrophages.
  • The mgtB, mgtR, and mgtU genes form a single transcript, allowing coordinated control of MgtB levels.
  • Small proteins can modulate transporter abundance to ensure pathogen homeostasis and survival.

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