Demonstration of a fusion mechanism between a fluid bactericidal liposomal formulation and bacterial cells.
It was previously demonstrated that fluid liposomal-encapsulated tobramycin, named Fluidosomes, was successful in eradicating mucoid Pseudomonas aeruginosa in an animal model of chronic pulmonary infection, whereas free antibiotic did not reduce colony-forming unit (CFU) counts (C. Beaulac et al., Antimicrob. Agents Chemother. 40 (1996) 665-669; C. Beaulac et al., J. Antimicrob. Chemother. 41 (1998) 35-41). These liposomes were also shown to be bactericidal in in vitro tests against strong resistant P. aeruginosa 64 microg/ml). The time needed to reach the maximal fusion rate was about 5 h for the resistant strain comparatively to much shorter time for the sensitive strain. The specific characteristics of Fluidosomes could help overcome bacterial resistance related to permeability barrier and even enzymatic hydrolysis considering the importance of synergy in the whole process of antibiotic resistance.
Sachetelli
S
S
Department of Microbiology and Immunology, Faculty of Medicine, University of Montreal, C.P. 6128, Succ. Centre-Ville, Montreal, Que., Canada.
Khalil
H
H
Chen
T
T
Beaulac
C
C
Sénéchal
S
S
Lagacé
J
J
D015060:1,2-Dipalmitoylphosphatidylcholine; D002462:Cell Membrane / Q000502:physiology / Q000648:ultrastructure; D005434:Flow Cytometry; D005456:Fluorescent Dyes; D007700:Kinetics; D008081:Liposomes; D008561:Membrane Fusion; D016253:Microscopy, Immunoelectron; D009930:Organic Chemicals; D010715:Phosphatidylglycerols; D011550:Pseudomonas aeruginosa / Q000502:physiology* / Q000648:ultrastructure; D014031:Tobramycin / Q000008:administration & dosage* / Q000493:pharmacokinetics*
D005456:Fluorescent Dyes; D008081:Liposomes; D009930:Organic Chemicals; C067882:PKH2-GL; D010715:Phosphatidylglycerols; D015060:1,2-Dipalmitoylphosphatidylcholine; C002773:dimyristoylphosphatidylglycerol; D014031:Tobramycin