Diffusion Retardation by Binding of Tobramycin in an Alginate Biofilm Model.
Microbial cells embedded in a self-produced extracellular biofilm matrix cause chronic infections, e. g. by Pseudomonas aeruginosa in the lungs of cystic fibrosis patients. The antibiotic killing of bacteria in biofilms is generally known to be reduced by 100-1000 times relative to planktonic bacteria. This makes such infections difficult to treat. We have therefore proposed that biofilms can be regarded as an independent compartment with distinct pharmacokinetics. To elucidate this pharmacokinetics we have measured the penetration of the tobramycin into seaweed alginate beads which serve as a model of the extracellular polysaccharide matrix in P. aeruginosa biofilm. We find that, rather than a normal first order saturation curve, the concentration of tobramycin in the alginate beads follows a power-law as a function of the external concentration. Further, the tobramycin is observed to be uniformly distributed throughout the volume of the alginate bead. The power-law appears to be a consequence of binding to a multitude of different binding sites. In a diffusion model these results are shown to produce pronounced retardation of the penetration of tobramycin into the biofilm. This filtering of the free tobramycin concentration inside biofilm beads is expected to aid in augmenting the survival probability of bacteria residing in the biofilm.
Department of Clinical Microbiology, Copenhagen University Hospital, Rigshospitalet, DK-2100 Copenhagen, Denmark.
Bao
B
Cao
Department of Clinical Microbiology, Copenhagen University Hospital, Rigshospitalet, DK-2100 Copenhagen, Denmark.
Lars
L
Christophersen
Department of Clinical Microbiology, Copenhagen University Hospital, Rigshospitalet, DK-2100 Copenhagen, Denmark.|Department of Immunology and Microbiology, UC-CARE, Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark.
Mette
0000-0001-5575-0384
M
Kolpen
Department of Clinical Microbiology, Copenhagen University Hospital, Rigshospitalet, DK-2100 Copenhagen, Denmark.
Peter Østrup
PØ
Jensen
Niels Bohr Institute, University of Copenhagen, Blegdamsvej 17, DK-2100 Copenhagen, Denmark.
Kim
K
Sneppen
Department of Clinical Microbiology, Copenhagen University Hospital, Rigshospitalet, DK-2100 Copenhagen, Denmark.|Department of Immunology and Microbiology, UC-CARE, Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark.
Niels
N
Høiby
Department of Clinical Microbiology, Copenhagen University Hospital, Rigshospitalet, DK-2100 Copenhagen, Denmark.
Claus
C
Moser
Biomedical Engineering, Dept. of Electrical Engineering, Technical University of Denmark, DK-2800 Lyngby, Denmark.
Thomas
0000-0002-6316-2539
T
Sams
D000464:Alginates; D000900:Anti-Bacterial Agents / Q000378:metabolism* / Q000493:pharmacokinetics; D018441:Biofilms; D020723:Glucuronic Acid; D006603:Hexuronic Acids; D008956:Models, Chemical; D014031:Tobramycin / Q000378:metabolism* / Q000493:pharmacokinetics
D000464:Alginates; D000900:Anti-Bacterial Agents; D006603:Hexuronic Acids; D020723:Glucuronic Acid; D014031:Tobramycin