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

Math Med Biol. 2014 Jun;31(2):179-204. doi: 10.1093/imammb/dqt003. Epub 2013 Mar 21.

Abstract

Lung failure due to chronic bacterial infection is the leading cause of death for patients with cystic fibrosis (CF). It is thought that the chronic nature of these infections is, in part, due to the increased tolerance and recalcitrant behaviour of bacteria growing as biofilms. Inhalation of silver carbene complex (SCC) antimicrobial, either encased in polymeric biodegradable particles or in aqueous form, has been proposed as a treatment. Through a coordinated experimental and mathematical modelling effort, we examine this proposed treatment of lung biofilms. Pseudomonas aeruginosa biofilms grown in a flow-cell apparatus irrigated with an artificial CF sputum medium are analysed as an in vitro model of CF lung infection. A 2D mathematical model of biofilm growth within the flow-cell is developed. Numerical simulations demonstrate that SCC inactivation by the environment is critical in aqueous SCC, but not SCC-polymer, based treatments. Polymer particle degradation rate is shown to be an important parameter that can be chosen optimally, based on environmental conditions and bacterial susceptibility.

Keywords: Pseudomonas aeruginosa; biofilm; cystic fibrosis; mathematical modelling; nanoparticle; silver carbene complex.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Biofilms / drug effects
  • Biofilms / growth & development*
  • Computer Simulation
  • Cystic Fibrosis / complications*
  • Cystic Fibrosis / immunology
  • Humans
  • In Vitro Techniques
  • Microscopy, Confocal
  • Models, Immunological*
  • Pseudomonas Infections / complications*
  • Pseudomonas Infections / drug therapy
  • Pseudomonas Infections / immunology
  • Pseudomonas aeruginosa / growth & development*
  • Pseudomonas aeruginosa / ultrastructure
  • Silver / administration & dosage
  • Silver / pharmacology*
  • Sputum / microbiology

Substances

  • Silver