Bismuth-ethanedithiol incorporated in a liposome-loaded tobramycin formulation modulates the alginate levels in mucoid Pseudomonas aeruginosa.
J Pharm Pharmacol
; 63(8): 999-1007, 2011 Aug.
Article
em En
| MEDLINE
| ID: mdl-21718282
ABSTRACT
OBJECTIVES:
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). KEYFINDINGS:
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pseudomonas aeruginosa
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Tobramicina
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Bismuto
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Biofilmes
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Alginatos
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Mercaptoetanol
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Antibacterianos
Idioma:
En
Revista:
J Pharm Pharmacol
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Canadá