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Magnesium homeostasis protects Salmonella against nitrooxidative stress

Travis J Bourret1, Lin Liu2, Jeff A Shaw3

  • 1Department of Medical Microbiology and Immunology, 2500 California Plaza, Creighton University, Criss I, Rm 521, Omaha, NE 68178, USA. TravisBourret@creighton.edu.

Scientific Reports
|November 10, 2017
PubMed

Insights

Salmonella PhoPQ system protects against reactive nitrogen species (RNS) by managing magnesium. This discovery reveals a key mechanism for bacterial survival during infection and antibiotic resistance.

Area of Science:

  • Microbiology
  • Bacterial Pathogenesis
  • Molecular Biology

Background:

  • The PhoPQ two-component system in Salmonella Typhimurium regulates responses to host environmental challenges like low Mg2+, pH, and antimicrobial peptides.
  • PhoPQ is crucial for Salmonella survival within macrophages and resistance to reactive nitrogen species (RNS) produced by host nitric oxide synthase.

Purpose of the Study:

  • To investigate the role of the PhoPQ system in Salmonella's resistance to RNS.
  • To elucidate the molecular mechanisms underlying PhoPQ-mediated protection against RNS-induced damage.

Main Methods:

  • Utilized Salmonella strains with phoPQ mutations to assess hypersensitivity to RNS in vitro.
  • Analyzed nitrotyrosine formation, [4Fe-4S] cluster oxidation, and DNA damage in response to RNS.
  • Investigated the role of respiratory NADH dehydrogenases and magnesium homeostasis via the MgtA transporter.

Main Results:

  • Salmonella strains lacking functional PhoPQ (∆phoQ) exhibited increased susceptibility to RNS killing, dependent on molecular oxygen.
  • This hypersensitivity correlated with nitrotyrosine formation, oxidation of dehydratase iron-sulfur clusters, and DNA damage.
  • Mutations in respiratory NADH dehydrogenases reduced RNS cytotoxicity against ∆phoQ Salmonella by limiting peroxynitrite formation.

Conclusions:

  • PhoPQ-dependent magnesium (Mg2+) homeostasis is critical for protecting Salmonella against nitrooxidative stress.
  • The PhoPQ system safeguards Salmonella from RNS damage, likely by maintaining Mg2+ homeostasis through the MgtA transporter.
  • Understanding this mechanism offers insights into Salmonella pathogenesis and potential therapeutic strategies targeting bacterial survival.

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