The Salmonella virulence protein MgtC promotes phosphate uptake inside macrophages

Area of Science:

• Microbiology
• Molecular Biology
• Pathogenesis

Background:

• The MgtC protein of Salmonella enterica is essential for survival within macrophages and virulence.
• MgtC is conserved in other intracellular pathogens like Mycobacterium tuberculosis.
• Few molecular targets of MgtC have been identified despite its importance.

Purpose of the Study:

• To identify the molecular targets of the MgtC virulence protein.
• To elucidate the mechanism by which MgtC contributes to pathogen survival and virulence.

Main Methods:

• Investigated the interaction between MgtC and PhoR histidine kinase.
• Assessed the effect of MgtC on phosphate transport.
• Utilized site-directed mutagenesis to study MgtC-PhoR binding and function.
• Compared the virulence of wild-type and mutant Salmonella in a mouse model.

Main Results:

• MgtC directly targets and activates the PhoR histidine kinase.
• This interaction leads to the activation of phosphate transport, independent of external phosphate levels.
• A specific amino acid change in PhoR disrupts MgtC binding and abrogates MgtC-mediated phosphate transport.
• Disabling MgtC's effect on phosphate transport unexpectedly increases Salmonella hypervirulence and reduces non-replicating populations in macrophages.

Conclusions:

• MgtC directly activates pathogen phosphate transport via PhoR.
• MgtC-mediated phosphate transport is essential for normal Salmonella pathogenesis, not just survival.
• This study reveals a novel mechanism of virulence factor action in intracellular bacterial infections.