PLGA nanoparticle-encapsulated lysostaphin for the treatment of Staphylococcus aureus infections

Guillermo Landa1, Laura Aguerri2, Silvia Irusta1

  • 1Instituto de Nanociencia y Materiales de Aragón (INMA), CSIC-Universidad de Zaragoza, 50009 Zaragoza, Spain; Department of Chemical and Environmental Engineering, University of Zaragoza, Campus Río Ebro-Edificio I+D, C/Poeta Mariano Esquillor S/N, 50018 Zaragoza, Spain; Aragon Health Research Institute (IIS Aragon), 50009 Zaragoza, Spain.

Insights

Novel nanoparticles effectively deliver the bacteriocin lysostaphin, enhancing its power against dangerous Staphylococcus aureus infections, including MRSA. This approach overcomes lysostaphin

Area of Science:

  • Microbiology
  • Biotechnology
  • Materials Science

Background:

  • Staphylococcus aureus, particularly methicillin-resistant strains (MRSA), causes severe infections with high mortality.
  • Existing treatments face challenges like antibiotic resistance and limited efficacy.
  • Lysostaphin shows potent anti-staphylococcal activity but has limitations in clinical use.

Purpose of the Study:

  • To develop and evaluate polylactic-co-glycolic acid (PLGA) nanoparticles for encapsulating lysostaphin.
  • To assess the enhanced antimicrobial efficacy of lysostaphin-loaded PLGA nanoparticles against Staphylococcus aureus.
  • To investigate the effectiveness of these nanoparticles in planktonic, biofilm, and intracellular infection models.

Main Methods:

  • Lysostaphin was encapsulated within biodegradable PLGA nanoparticles.
  • Antimicrobial activity was tested against various Staphylococcus aureus strains, including GFP-expressing strains for traceability.
  • Efficacy was evaluated in planktonic, biofilm, and in vitro intracellular infection models.

Main Results:

  • Lysostaphin-loaded PLGA nanoparticles demonstrated significant bacterial viability reduction in planktonic and biofilm states.
  • The nanoparticles showed enhanced efficacy in an in vitro intracellular infection model compared to free lysostaphin.
  • Successful encapsulation and sustained release properties of PLGA nanoparticles were observed.

Conclusions:

  • PLGA nanoparticle encapsulation enhances the therapeutic potential of lysostaphin against Staphylococcus aureus.
  • This novel delivery system overcomes limitations of free lysostaphin, offering a promising strategy for treating staphylococcal infections.
  • The developed nanoparticles show potential for improved treatment of both extracellular and intracellular S. aureus infections.