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Fighting fibrin with fibrin: Vancomycin delivery into coagulase-mediated Staphylococcus aureus biofilms via
Grant Scull1,2, Adrian Aligwekwe1,2, Ysabel Rey1,2
1Joint Department of Biomedical Engineering, NC State University and UNC-Chapel Hill, Raleigh, North Carolina, USA.
Abstract:
Staphylococcus aureus skin and soft tissue infection is a common ailment placing a large burden upon global healthcare infrastructure. These bacteria are growing increasingly recalcitrant to frontline antimicrobial therapeutics like vancomycin due to the prevalence of variant populations such as methicillin-resistant and vancomycin-resistant strains, and there is currently a dearth of novel antibiotics in production. Additionally, S. aureus has the capacity to hijack the host clotting machinery to generate fibrin-based biofilms that confer protection from host antimicrobial mechanisms and antibiotic-based therapies, enabling immune system evasion and significantly reducing antimicrobial efficacy. Emphasis is being placed on improving the effectiveness of therapeutics that are already commercially available through various means. Fibrin-based nanoparticles (FBNs) were developed and found to interact with S. aureus through the clumping factor A (ClfA) fibrinogen receptor and directly integrate into the biofilm matrix. FBNs loaded with antimicrobials such as vancomycin enabled a targeted and sustained release of antibiotic that increased drug contact time and reduced the therapeutic dose required for eradicating the bacteria, both in vitro and in vivo. Collectively, these findings suggest that FBN-antibiotic delivery may be a novel and potent therapeutic tool for the treatment of S. aureus biofilm infections.
Insights
Fibrin-based nanoparticles loaded with vancomycin effectively target Staphylococcus aureus biofilms. This novel delivery system enhances antibiotic efficacy against resistant strains, reducing required doses for bacterial eradication.
Area of Science:
- Microbiology
- Biotechnology
- Pharmacology
Background:
- Staphylococcus aureus infections pose a significant global health burden.
- Increasing antimicrobial resistance, including methicillin-resistant and vancomycin-resistant strains, limits treatment options.
- S. aureus forms protective fibrin-based biofilms by hijacking host clotting factors, hindering conventional therapies.
Purpose of the Study:
- To investigate the potential of fibrin-based nanoparticles (FBNs) as a drug delivery system for S. aureus infections.
- To evaluate the efficacy of FBNs loaded with vancomycin in combating S. aureus biofilms.
- To explore FBNs' interaction with S. aureus and their integration into biofilm structures.
Main Methods:
- Development of fibrin-based nanoparticles (FBNs).
- Assessment of FBN interaction with Staphylococcus aureus via clumping factor A (ClfA).
- Evaluation of vancomycin-loaded FBNs for targeted delivery and sustained release in vitro and in vivo.
- Analysis of biofilm eradication efficacy and required therapeutic dose reduction.
Main Results:
- FBNs demonstrated interaction with S. aureus through the ClfA receptor.
- FBNs were successfully integrated into the S. aureus fibrin-based biofilm matrix.
- Vancomycin-loaded FBNs facilitated targeted and sustained antibiotic release.
- This approach increased antibiotic contact time and reduced the effective therapeutic dose for bacterial eradication.
- Efficacy was confirmed in both in vitro and in vivo models.
Conclusions:
- Fibrin-based nanoparticles represent a promising strategy for enhancing antibiotic delivery against S. aureus.
- FBN-antibiotic conjugates effectively target and disrupt S. aureus biofilms.
- This novel therapeutic approach holds potential for treating challenging S. aureus biofilm infections, especially those involving resistant strains.
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