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Mathematical Modeling of Pseudomonas aeruginosa Biofilm Growth and Treatment in the Cystic Fibrosis Lung

Miller, James Kyle

Abstract Details

2012, Doctor of Philosophy, University of Akron, Integrated Bioscience.
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 behavior of bacteria growing as biofilms. Inhalation of Silver Carbene Complex (SCC) antimicrobial, either encased in L-tyrosine polyphosphate (LTP) particles or in aqueous form, has been proposed as a treatment. Through a coordinated experimental and mathematical modeling effort, this dissertation examines this proposed treatment of lung biofilms. Pseudomonas aeruginosa biofilms grown in a flow-cell apparatus irrigated with an artificial CF sputum medium are analyzed 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-LTP, based treatments. LTP particle degradation rate is shown to be a tunable parameter that can be chosen optimally, based on environmental conditions and bacterial susceptibility. In addition, a 2D model of mushroom-like morphology and cavity formation in Pseudomonas aeruginosa biofilms is developed. Iron-signaling is proposed as a plausible mechanism for cavity formation.
Gerald Young, Dr. (Advisor)
Curtis Clemons, Dr. (Committee Member)
Kevin Kreider, Dr. (Committee Member)
Patrick Wilber, Dr. (Committee Member)
Yun Yang, Dr. (Committee Member)
Amy Milsted, Dr. (Committee Member)
238 p.

Recommended Citations

Citations

  • Miller, J. K. (2012). Mathematical Modeling of Pseudomonas aeruginosa Biofilm Growth and Treatment in the Cystic Fibrosis Lung [Doctoral dissertation, University of Akron]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=akron1342031801

    APA Style (7th edition)

  • Miller, James. Mathematical Modeling of Pseudomonas aeruginosa Biofilm Growth and Treatment in the Cystic Fibrosis Lung. 2012. University of Akron, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=akron1342031801.

    MLA Style (8th edition)

  • Miller, James. "Mathematical Modeling of Pseudomonas aeruginosa Biofilm Growth and Treatment in the Cystic Fibrosis Lung." Doctoral dissertation, University of Akron, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=akron1342031801

    Chicago Manual of Style (17th edition)