Novel Treatment of Staphylococcus aureus Device-Related Infections Using Fibrinolytic Agents

Area of Science:

• Microbiology
• Biotechnology
• Infectious Diseases

Background:

• Staphylococcal infections with biofilms pose treatment challenges, particularly for device-related infections.
• Staphylococcus aureus biofilms are regulated by SaeRS and fibrinogen conversion to fibrin on plasma-coated surfaces.

Purpose of the Study:

• To investigate the efficacy of fibrinolytic agents in digesting the fibrin biofilm matrix of S. aureus.
• To evaluate the combined effect of fibrinolytic agents and antimicrobials against S. aureus biofilms in vitro and in vivo.
• To assess the safety profile of fibrinolytic agents regarding cytotoxicity and host immune response.

Main Methods:

• In vitro treatment of S. aureus biofilms using fibrinolytic agents (plasmin, streptokinase, nattokinase, TrypLE) with and without antimicrobials.
• In vivo efficacy evaluation in a rat model of intravascular catheter infection.
• Assessment of cytotoxicity and cytokine response in whole human blood.

Main Results:

• Fibrinolytic agents effectively dispersed established S. aureus biofilms under biomimetic conditions.
• Combinations of fibrinolytic agents and antimicrobials effectively killed released bacterial cells.
• TrypLE and nattokinase demonstrated superior removal of adherent cells and enhanced antimicrobial efficacy in vitro and in vivo.
• Fibrinolytic agents showed no cytotoxicity and did not impact the host immune response.

Conclusions:

• Fibrinolytic agents, particularly TrypLE and nattokinase, are effective in dispersing S. aureus biofilms.
• These agents significantly enhance the efficacy of existing antimicrobials against device-related staphylococcal infections.
• Fibrinolytic agents represent a promising therapeutic strategy for treating S. aureus device-related infections.