Reduced adherence and host cell invasion by methicillin-resistant Staphylococcus aureus expressing the surface...

Area of Science:

• Microbiology
• Infectious Diseases
• Bacterial Pathogenesis

Background:

• Methicillin-resistant Staphylococcus aureus (MRSA) poses a significant threat due to its ability to invade host cells.
• Staphylococcus aureus invasion relies on the interaction between bacterial fibronectin-binding proteins and host cell beta(1)-integrins.
• The role of the surface protein Plague (Pls) in MRSA adhesion and invasion requires further elucidation.

Purpose of the Study:

• To investigate the impact of the Pls surface protein on the adhesion and invasion capabilities of clinical MRSA strains.
• To compare the adhesive and invasive properties of Pls-positive (Pls(+)) and Pls-negative (Pls(-)) MRSA strains.
• To determine the specific contribution of Pls to MRSA's interaction with host extracellular matrix components.

Main Methods:

• Comparative analysis of adhesion and binding assays using immobilized and soluble fibronectin (Fn), fibrinogen (Fg), immunoglobulin G (IgG), and laminin.
• Quantification of MRSA invasion into 293 cells.
• Genetic manipulation of the pls gene in MRSA strain 1061 (gene disruption and complementation).

Main Results:

• Pls-positive MRSA strains exhibited significantly reduced adhesion to immobilized Fn, Fg, IgG, and laminin compared to Pls-negative strains.
• Binding to soluble Fn and Fg was less efficient in Pls(+) strains, while soluble IgG binding was comparable.
• Pls(+) strains demonstrated markedly lower invasiveness into 293 cells than Pls(-) strains.
• Disruption of the pls gene enhanced invasiveness but did not alter binding to soluble Fn, Fg, or IgG.
• Complementation restored invasiveness but not the reduced adhesion to immobilized Fn.

Conclusions:

• The expression of the Pls surface protein in MRSA is generally correlated with reduced bacterial adhesiveness and invasiveness.
• Pls appears to play a crucial role in limiting MRSA's ability to adhere to and invade host cells, particularly through interactions with immobilized extracellular matrix proteins.