Bactericidal effect of gentamicin-induced membrane vesicles derived from Pseudomonas aeruginosa PAO1 on gram-positive

Kelly L MacDonald1, Terry J Beveridge

  • 1Canadian Bacterial Diseases Network, National Centre of Excellence and Department of Microbiology, College of Biological Sciences, University of Guelph, Guelph, ON N1G 2W1, Canada.

Insights

Gentamicin-induced membrane vesicles (g-MVs) show therapeutic potential against some gram-positive bacteria by utilizing both gentamicin and autolysin. These g-MVs demonstrate enhanced efficacy compared to soluble gentamicin for specific bacterial infections.

Area of Science:

  • Microbiology
  • Bacteriology
  • Drug Delivery Systems

Background:

  • Pseudomonas aeruginosa PAO1 produces gentamicin-induced membrane vesicles (g-MVs).
  • g-MVs contain both the antibiotic gentamicin and a potent peptidoglycan hydrolase (PGase; autolysin).
  • g-MVs have previously shown efficacy against gram-negative pathogens.

Purpose of the Study:

  • To evaluate the therapeutic potential of g-MVs against four gram-positive bacteria.
  • To compare the efficacy of g-MVs with soluble gentamicin.
  • To investigate the mechanism of g-MV interaction with gram-positive bacterial cell surfaces.

Main Methods:

  • Bactericidal assays were performed against Bacillus subtilis, Staphylococcus aureus, Listeria monocytogenes, and Enterococcus hirae.
  • Electron microscopy was used to examine thin sections of bacteria treated with g-MVs.
  • Hydrophobic interaction chromatography and zymograms were employed to analyze MV attachment and autolysin activity.

Main Results:

  • Bacillus subtilis and Staphylococcus aureus were susceptible to g-MV killing, while Listeria monocytogenes showed slight susceptibility, and Enterococcus hirae was unaffected.
  • g-MVs were generally more effective than soluble gentamicin.
  • MV attachment varied based on bacterial surface hydrophobicity, and autolysin activity was observed in most tested organisms except E. hirae.

Conclusions:

  • g-MVs exhibit selective bactericidal activity against certain gram-positive bacteria.
  • The dual action of gentamicin and autolysin contributes to g-MV efficacy.
  • g-MVs represent a promising therapeutic strategy for specific gram-positive bacterial infections, warranting further investigation.

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