title: Bismuth-ethanedithiol incorporated in a liposome-loaded tobramycin formulation modulates the alginate levels in mucoid Pseudomonas aeruginosa.
abstract: OBJECTIVE
  This study examined the antibacterial activity, alginate modulation, and deposition of a tobramycin bismuth-ethanedithiol (Tob-Bi) conventional (free) or vesicle-entrapped (lipo) formulation against two mucoid Pseudomonas aeruginosa clinical isolates.
  
  
  METHODS
  The inhibitory, bactericidal and biofilm eradication concentrations (in presence or absence of alginate lyase) were determined. The modulation of alginate was assessed by the carbazole assay and fluorescent-labelling of live alginate-producing biofilms by confocal microscopy. The deposition of the formulations was assessed using the immunogold-labelling technique, transmission electron microscopy, and energy dispersive X-ray spectroscopy (EDS).
  
  
  RESULTS
  The inhibitory and bactericidal concentrations for lipo Tob-Bi compared with free Tob-Bi were reduced in all strains by 2- to 8-fold, and 2- to 32-fold, respectively. The biofilm eradication concentrations for lipo Tob-Bi compared with free Tob-Bi were reduced by 4- to 32-fold in the mucoid strains. The addition of alginate lyase transiently enhanced eradication for one mucoid strain only. The alginate levels were attenuated by more than half, and free Tob-Bi fared better than lipo Tob-Bi determined by the carbazole assay. Under confocal microscopy, alginate lyase reduced alginate levels and detached mucoid biofilms. Free and lipo Tob-Bi did not detach the bacteria from the surface, but attenuated alginate levels. Tobramycin was detected by immunogold-labelling inside the bacterium, but EDS did not detect bismuth deposits.
  
  
  CONCLUSIONS
  These findings substantiate a role in which tobramycin, bismuth, and alginate lyase play in eradicating mucoid P. aeruginosa growth and modulate alginate levels.
authors: Department of Biomolecular Sciences, Laurentian University, Sudbury Medical Sciences Division, Sudbury, Ontario, Canada.
authors: Misagh
authors: M
authors: Alipour
authors: Crystal
authors: C
authors: Dorval
authors: Zacharias E
authors: ZE
authors: Suntres
authors: Abdelwahab
authors: A
authors: Omri
mesh_terms: D000464:Alginates / Q000378:metabolism*; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000494:pharmacology; D018441:Biofilms / Q000187:drug effects*; D001729:Bismuth / Q000008:administration & dosage / Q000494:pharmacology*; D004338:Drug Combinations; D008081:Liposomes; D008190:Lyases / Q000494:pharmacology; D008623:Mercaptoethanol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000378:metabolism; D014031:Tobramycin / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D000464:Alginates; D000900:Anti-Bacterial Agents; D004338:Drug Combinations; D008081:Liposomes; D008623:Mercaptoethanol; C031854:1,2-ethanedithiol; D008190:Lyases; D001729:Bismuth; D014031:Tobramycin