Flotillin scaffold activity contributes to type VII secretion system assembly in Staphylococcus aureus.

Area of Science:

• Microbiology
• Molecular Biology
• Biochemistry

Background:

• Scaffold proteins are crucial for organizing multi-enzymatic complexes in eukaryotes, but their roles in prokaryotes are less understood.
• Bacterial functional membrane microdomains (FMM), analogous to eukaryotic lipid rafts, contain scaffold proteins like flotillin.
• Flotillin is hypothesized to facilitate protein interactions within bacterial FMM.

Purpose of the Study:

• To investigate the scaffold activity of the flotillin homolog FloA in Staphylococcus aureus.
• To determine FloA's role in the assembly and function of the type VII secretion system (T7SS).
• To explore small molecules that modulate flotillin's scaffold activity and T7SS function.

Main Methods:

• Biochemical approaches were used to study FloA's scaffold activity.
• Staphylococcus aureus strains with and without FloA were analyzed for T7SS function.
• In vitro and in vivo assays were performed to test the effect of small molecules on flotillin and T7SS.

Main Results:

• Staphylococcus aureus lacking FloA exhibited reduced type VII secretion system function and effector secretion.
• Flotillin was found to mediate intermolecular interactions among T7SS proteins.
• Small molecules interfering with flotillin scaffold activity altered T7SS function both in vitro and in vivo.

Conclusions:

• Flotillin (FloA) acts as a scaffold protein in Staphylococcus aureus, supporting type VII secretion system assembly and function.
• Flotillin influences the interactions of membrane proteins involved in bacterial infection.
• Targeting flotillin scaffold activity presents a potential strategy to modulate the infective potential of Staphylococcus aureus.