Abstract
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.
Highlights
Aggregates of microbial cells embedded in a self-produced extracellular matrix, otherwise known as biofilm, lead to chronic and recurrent infections, e. g. by Pseudomonas aeruginosa bacteria in the lungs of cystic fibrosis (CF) patients, which are difficult to treat [1]
The biofilm matrix itself may act as a barrier retarding the diffusion of antibiotics into biofilms as seen in a recent study of tobramycin penetration into non-mucoid P. aeruginosa biofilm [2]
The power law was found to be consistent with nonspecific binding to sites in the polyanion biofilm matrix
Summary
Aggregates of microbial cells embedded in a self-produced extracellular matrix, otherwise known as biofilm, lead to chronic and recurrent infections, e. g. by Pseudomonas aeruginosa bacteria in the lungs of cystic fibrosis (CF) patients, which are difficult to treat [1]. The biofilm mode of growth provides protection of the microbial cells making them significantly less susceptible to antimicrobial treatment compared to their planktonic counterparts [2]. The biofilm matrix itself may act as a barrier retarding the diffusion of antibiotics into biofilms as seen in a recent study of tobramycin penetration into non-mucoid P. aeruginosa biofilm [2]. Due to these physiological properties of biofilms, distinct from the surrounding tissue during biofilm infections, Cao et al suggested that biofilms with their matrix form a third and independent compartment with exclusive pharmacokinetics important for the effect of antibiotics [4]. If the pharmacokinetics of an antibiotic within the biofilm is very particular, this effect could be substantial even in relatively small biofilms and contribute to the observed reduced bacterial killing inside biofilms
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