Diffusion Retardation by Binding of Tobramycin in an Alginate Biofilm Model

• Published in: PloS one Vol. 11; no. 4; p. e0153616
• Main Authors: Cao, Bao, Christophersen, Lars, Kolpen, Mette, Jensen, Peter Østrup, Sneppen, Kim, Høiby, Niels, Moser, Claus, Sams, Thomas
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 21.04.2016; Public Library of Science (PLoS)
• Subjects: Alginates; Alginic acid; Anti-Bacterial Agents - metabolism; Anti-Bacterial Agents - pharmacokinetics; Antibiotics; Antimicrobial agents; Bacteria; Beads; Binding sites; Bioengineering; Biofilms; Biology and Life Sciences; Chemotherapy; Cystic fibrosis; Diffusion; Experiments; Fibrosis; Filtration; Genetic aspects; Glucuronic Acid; Health sciences; Hexuronic Acids; Immunology; Infections; Lungs; Medicine and Health Sciences; Microbial mats; Microorganisms; Models, Chemical; Penetration; Pharmacokinetics; Pharmacology; Physiological aspects; Power law; Pseudomonas aeruginosa; Tobramycin; Tobramycin - metabolism; Tobramycin - pharmacokinetics; Trends; Denmark; United States > US; Massachusetts
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0153616

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.