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Published on: January 27, 2021
Interplay between MgtC and PagC in Salmonella enterica serovar Typhimurium
Eric Alix1, Tsuyoshi Miki, Christine Felix
1Inserm, ESPRI 26, Avenue J.F. Kennedy, 30908 Nîmes Cedex 02, France.
Abstract:
In Salmonella enterica serovar Typhimurium, MgtC and PagC are positively regulated by the PhoP-PhoQ two-component system, which is activated under magnesium deprivation. Both MgtC and PagC are of unknown function but have been involved in intramacrophage survival. We have found that the amount of PagC is lowered in a DeltamgtC mutant strain grown in magnesium depleted medium. However, the effect of MgtC on PagC does not account for the growth defect of a DeltamgtC mutant in macrophages since, in contrast to previous reports, our results indicate that PagC does not contribute to intramacrophage survival. In addition, a pagC null mutant is only poorly attenuated in Nramp1-negative or Nramp1-positive mice. On the other hand, a mgtC null mutant is significantly more attenuated with Nramp1-positive than Nramp1-negative mice, suggesting that a functional Nramp1 (Slc11a1) further limits the multiplication of this mutant within the host.
Insights
The MgtC protein in Salmonella Typhimurium impacts PagC levels and intramacrophage survival. A functional Nramp1 protein limits MgtC mutant multiplication within host cells.
Area of Science:
- Microbiology
- Bacterial Pathogenesis
- Host-Pathogen Interactions
Background:
- The PhoP-PhoQ system regulates Salmonella enterica serovar Typhimurium virulence under magnesium deprivation.
- MgtC and PagC proteins are regulated by PhoP-PhoQ and implicated in intramacrophage survival, though their functions are unclear.
Purpose of the Study:
- To investigate the functional relationship between MgtC and PagC in Salmonella Typhimurium.
- To determine the role of MgtC and PagC in intramacrophage survival.
- To assess the influence of Nramp1 on the virulence of mgtC and pagC mutants.
Main Methods:
- Generating and analyzing DeltamgtC and pagC null mutant strains of Salmonella Typhimurium.
- Assessing bacterial growth and survival in magnesium-depleted media and within macrophages.
- Evaluating mutant attenuation in Nramp1-positive and Nramp1-negative mouse models.
Main Results:
- DeltamgtC mutant showed decreased PagC levels in magnesium-depleted medium.
- PagC did not contribute to intramacrophage survival, and pagC null mutants were poorly attenuated in mice.
- MgtC null mutants were significantly more attenuated in Nramp1-positive mice compared to Nramp1-negative mice.
Conclusions:
- MgtC influences PagC expression but not intramacrophage survival.
- Nramp1 (Slc11a1) plays a crucial role in limiting Salmonella mgtC mutant proliferation within the host.
- The function of PagC in Salmonella virulence remains to be elucidated.
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