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A Non-Coding Small RNA MicC Contributes to Virulence in Outer Membrane Proteins in Salmonella Enteritidis
Published on: January 27, 2021
Peptide-assisted degradation of the Salmonella MgtC virulence factor
Eric Alix1, Anne-Béatrice Blanc-Potard
1Inserm, ESPRI 26, Nîmes, France.
Abstract:
MgtC is a virulence factor common to several intracellular pathogens that is required for intramacrophage survival and growth in magnesium-depleted medium. In Salmonella enterica, MgtC is coexpressed with the MgtB magnesium transporter and transcription of the mgtCB operon is induced by magnesium deprivation. Despite the high level of mgtCB transcriptional induction in magnesium-depleted medium, the MgtC protein is hardly detected in a wild-type Salmonella strain. Here, we show that downregulation of MgtC expression is dependent on a hydrophobic peptide, MgtR, which is encoded by the mgtCB operon. Our results suggest that MgtR promotes MgtC degradation by the FtsH protease, providing a negative regulatory feedback. Bacterial two-hybrid assays demonstrate that MgtR interacts with the inner-membrane MgtC protein. We identified mutant derivatives of MgtR and MgtC that prevent both regulation and interaction between the two partners. In macrophages, overexpression of the MgtR peptide led to a decrease of the replication rate of Salmonella. This study highlights the role of peptides in bacterial regulatory mechanisms and provides a natural antagonist of the MgtC virulence factor.
Insights
A novel peptide, MgtR, regulates the MgtC virulence factor in Salmonella by promoting its degradation. This discovery reveals a new bacterial regulatory mechanism and a potential target for combating intracellular pathogens.
Area of Science:
- Microbiology
- Molecular Biology
- Pathogenesis
Background:
- MgtC is a crucial virulence factor for intracellular pathogens, essential for survival within macrophages under magnesium-depleted conditions.
- In Salmonella enterica, MgtC is co-transcribed with the MgtB magnesium transporter, with expression upregulated during magnesium deprivation.
Purpose of the Study:
- To elucidate the mechanism behind the low detection of MgtC protein despite high transcriptional levels in magnesium-depleted Salmonella.
- To investigate the role of the MgtR peptide in regulating MgtC expression and virulence.
Main Methods:
- Bacterial two-hybrid assays to study MgtR and MgtC interactions.
- Analysis of MgtR and MgtC mutant derivatives.
- In vivo studies involving Salmonella replication rates in macrophages.
Main Results:
- MgtR, a hydrophobic peptide encoded by the mgtCB operon, downregulates MgtC expression.
- MgtR promotes the degradation of MgtC via the FtsH protease, establishing a negative feedback loop.
- MgtR directly interacts with the MgtC protein, and specific mutations disrupt this interaction and regulation.
- Overexpression of MgtR in macrophages reduced Salmonella replication.
Conclusions:
- Peptides play significant roles in bacterial regulatory networks.
- MgtR acts as a natural antagonist to the MgtC virulence factor, offering insights into pathogen control strategies.
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