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Intracellular phase for an extracellular bacterial pathogen: MgtC shows the way
Audrey Bernut1, Claudine Belon1, Chantal Soscia2
1Laboratoire de Dynamique des Interactions Membranaires Normales et Pathologiques, Université de Montpellier (DIMNP CNRS-UMR5235), Place Eugène Bataillon, 34095 Montpellier Cedex 05, France.
Abstract:
Pseudomonas aeruginosa is an extracellular pathogen known to impair host phagocytic functions. However, our recent results identify MgtC as a novel actor in P. aeruginosa virulence, which plays a role in an intramacrophage phase of this pathogen. In agreement with its intracellular function, P. aeruginosamgtC gene expression is strongly induced when the bacteria reside within macrophages. MgtC was previously known as a horizontally-acquired virulence factor important for multiplication inside macrophages in several intracellular bacterial pathogens. MgtC thus provides a singular example of a virulence determinant that subverts macrophages both in intracellular and extracellular pathogens. Moreover, we demonstrate that P. aeruginosa MgtC is required for optimal growth in Mg2+ deprived medium, a property shared by MgtC factors from intracellular pathogens and, under Mg2+ limitation, P. aeruginosa MgtC prevents biofilm formation. We propose that MgtC has a similar function in intracellular and extracellular pathogens, which contributes to macrophage resistance and fine-tune adaptation to the host in relation to the different bacterial lifestyles. MgtC thus appears as an attractive target for antivirulence strategies and our work provides a natural peptide as MgtC antagonist, which paves the way for the development of MgtC inhibitors.
Insights
Pseudomonas aeruginosa utilizes MgtC to survive within macrophages, a novel virulence factor also aiding growth in low magnesium and preventing biofilm formation. This discovery offers new antivirulence strategies targeting MgtC.
Area of Science:
- Microbiology
- Pathogen-host interactions
- Bacterial virulence factors
Background:
- Pseudomonas aeruginosa is primarily an extracellular pathogen.
- MgtC is a known virulence factor in intracellular bacterial pathogens, aiding multiplication within macrophages.
- The role of MgtC in P. aeruginosa, particularly in its intramacrophage phase, was previously uncharacterized.
Purpose of the Study:
- To investigate the novel role of MgtC in Pseudomonas aeruginosa virulence.
- To understand the function of MgtC during the intramacrophage phase of P. aeruginosa.
- To explore MgtC as a potential target for antivirulence strategies.
Main Methods:
- Analysis of P. aeruginosa mgtC gene expression within macrophages.
- Investigating the growth of P. aeruginosa in magnesium-deprived media.
- Assessing the impact of MgtC on biofilm formation under magnesium limitation.
- Identification of a natural peptide antagonist for MgtC.
Main Results:
- P. aeruginosa mgtC gene expression is significantly induced within macrophages.
- MgtC is essential for P. aeruginosa optimal growth in magnesium-deprived conditions.
- MgtC inhibits biofilm formation in P. aeruginosa when magnesium is limited.
- A natural peptide was identified as an MgtC antagonist.
Conclusions:
- MgtC is a dual-acting virulence factor, functioning in both intracellular and extracellular phases of P. aeruginosa.
- MgtC contributes to macrophage resistance and bacterial adaptation to host environments.
- MgtC represents a promising target for developing novel antivirulence therapies and inhibitors.