Modeling the response of a biofilm to silver-based antimicrobial

Abstract

Biofilms are found within the lungs of patients with chronic pulmonary infections, in particular patients with cystic fibrosis, and are the major cause of morbidity and mortality for these patients. The work presented here is part of a large interdisciplinary effort to develop an effective drug delivery system and treatment strategy to kill biofilms growing in the lung. The treatment strategy exploits silver-based antimicrobials, in particular, silver carbene complexes (SCC). This manuscript presents a mathematical model describing the growth of a biofilm and predicts the response of a biofilm to several basic treatment strategies. The continuum model is composed of a set of reaction-diffusion equations for the transport of soluble components (nutrient and antimicrobial), coupled to a set of reaction-advection equations for the particulate components (living, inert, and persister bacteria, extracellular polymeric substance, and void). We explore the efficacy of delivering SCC both in an aqueous solution and in biodegradable polymer nanoparticles. Minimum bactericidal concentration (MBC) levels of antimicrobial in both free and nanoparticle-encapsulated forms are estimated. Antimicrobial treatment demonstrates a biphasic killing phenomenon, where the active bacterial population is killed quickly followed by a slower killing rate, which indicates the presence of a persister population. Finally, our results suggest that a biofilm with a ready supply of nutrient throughout its depth has fewer persister bacteria and hence may be easier to treat than one with less nutrient.

Mathematical modelling of Pseudomonas aeruginosa biofilm growth and treatment in the cystic fibrosis lung

“…The addition of fluid flow over the biofilm as a mechanism for nutrient and SCC transport represents an extension of Stine et al (2012). Stine et al (2012) showed that 10 9 particles per ml of biofilm is able to surpass the MIC in a Bacillus anthracis biofilm.…”

“…Stine et al (2012) showed that 10 9 particles per ml of biofilm is able to surpass the MIC in a Bacillus anthracis biofilm. This particle density is similar to that used in the model presented here, but is shown to effectively treat a biofilm with an MIC 10 times higher than that of P. aeruginosa used here.…”

“…This particle density is similar to that used in the model presented here, but is shown to effectively treat a biofilm with an MIC 10 times higher than that of P. aeruginosa used here. Stine et al (2012) represents an investigation of the ideal case. That is, no flux conditions result in all of the SCCs released from polymer particles remaining within the biofilm.…”

“…Miller et al (2013) considered biofilm-particle interaction in a flow-cell environment. Stine et al (2012) estimated what LTP particle concentrations one might have to achieve to reach a known minimal inhibitory concentration (MIC) value for the SCC drug. The authors assumed a no flux condition at the biofilm-fluid interface, which can be viewed as a best-case scenario for estimating dosing.…”

Positive computational modelling of the dynamics of active and inert biomass with extracellular polymeric substances

“…As well-known examples of the thread that biological films represent to human health, we may cite the recognition of the colonization of some bacterial colonies in chronic wounds [22], the persistence of certain bacterial infections associated with foreign bodies due to the formation of biological films [18], the growth of infectious microbial colonies in endourological devices [34], just to mention some health-related conditions derived from the growth of biological colonies. It is worth mentioning that many other realistic problems also involve the investigation of biological films, such as the biological treatment of polluted fluids [3,4,13,20], the development of microbial fuel cells to generate electrical power [19,24,25,37], the design of biological sensors [5,35], among other applications [32].…”