title: Mathematical modelling of Pseudomonas aeruginosa biofilm growth and treatment in the cystic fibrosis lung.
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.
authors.affiliation: Integrated Bioscience, University of Akron, Akron, OH, USA jkm29@zips.uakron.edu.
authors.forename: J K
authors.initials: JK
authors.lastname: Miller
authors.affiliation: Integrated Bioscience, University of Akron, Akron, OH, USA.
authors.forename: Justin S
authors.initials: JS
authors.lastname: Brantner
authors.affiliation: Integrated Bioscience, University of Akron, Akron, OH, USA.
authors.forename: Curtis
authors.initials: C
authors.lastname: Clemons
authors.affiliation: Integrated Bioscience, University of Akron, Akron, OH, USA.
authors.forename: K L
authors.initials: KL
authors.lastname: Kreider
authors.affiliation: Integrated Bioscience, University of Akron, Akron, OH, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Milsted
authors.affiliation: Integrated Bioscience, University of Akron, Akron, OH, USA.
authors.forename: Pat
authors.initials: P
authors.lastname: Wilber
authors.affiliation: Integrated Bioscience, University of Akron, Akron, OH, USA.
authors.forename: Yang H
authors.initials: YH
authors.lastname: Yun
authors.affiliation: Integrated Bioscience, University of Akron, Akron, OH, USA.
authors.forename: Wiley J
authors.initials: WJ
authors.lastname: Youngs
authors.affiliation: Integrated Bioscience, University of Akron, Akron, OH, USA.
authors.forename: Gerald
authors.initials: G
authors.lastname: Young
authors.affiliation: Department of Biology, University of Akron, Akron, OH, USA.
authors.forename: Hope T
authors.initials: HT
authors.lastname: Badawy
authors.affiliation: Department of Biology, University of Akron, Akron, OH, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Milsted
authors.affiliation: Department of Mathematics, University of Akron, Akron, OH, USA.
authors.forename: Curtis
authors.initials: C
authors.lastname: Clemons
authors.affiliation: Department of Mathematics, University of Akron, Akron, OH, USA.
authors.forename: K L
authors.initials: KL
authors.lastname: Kreider
authors.affiliation: Department of Mathematics, University of Akron, Akron, OH, USA.
authors.forename: Pat
authors.initials: P
authors.lastname: Wilber
authors.affiliation: Department of Mathematics, University of Akron, Akron, OH, USA.
authors.forename: Gerald
authors.initials: G
authors.lastname: Young
authors.affiliation: Department of Biomedical Engineering, University of Akron, Akron, OH, USA.
authors.forename: Yang H
authors.initials: YH
authors.lastname: Yun
authors.affiliation: Department of Chemistry, University of Akron, Akron, OH, USA.
authors.forename: Patrick O
authors.initials: PO
authors.lastname: Wagers
authors.affiliation: Department of Chemistry, University of Akron, Akron, OH, USA.
authors.forename: Wiley J
authors.initials: WJ
authors.lastname: Youngs
mesh_terms: D018441:Biofilms / Q000187:drug effects / Q000254:growth & development*; D003198:Computer Simulation; D003550:Cystic Fibrosis / Q000150:complications* / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D018613:Microscopy, Confocal; D018448:Models, Immunological; D011552:Pseudomonas Infections / Q000150:complications* / Q000188:drug therapy / Q000276:immunology; D011550:Pseudomonas aeruginosa / Q000254:growth & development* / Q000648:ultrastructure; D012834:Silver / Q000008:administration & dosage / Q000494:pharmacology*; D013183:Sputum / Q000382:microbiology
chemical_list: D012834:Silver
keywords: Pseudomonas aeruginosa; biofilm; cystic fibrosis; mathematical modelling; nanoparticle; silver carbene complex