title: Mathematical modeling of dormant cell formation in growing biofilm.
abstract: Understanding the dynamics of dormant cells in microbial biofilms, in which the bacteria are embedded in extracellular matrix, is important for developing successful antibiotic therapies against pathogenic bacteria. Although some of the molecular mechanisms leading to bacterial persistence have been speculated in planktonic bacterial cell, how dormant cells emerge in the biofilms of pathogenic bacteria such as Pseudomonas aeruginosa remains unclear. The present study proposes four hypotheses of dormant cell formation; stochastic process, nutrient-dependent, oxygen-dependent, and time-dependent processes. These hypotheses were implemented into a three-dimensional individual-based model of biofilm formation. Numerical simulations of the different mechanisms yielded qualitatively different spatiotemporal distributions of dormant cells in the growing biofilm. Based on these simulation results, we discuss what kinds of experimental studies are effective for discriminating dormant cell formation mechanisms in biofilms.
authors.affiliation: Department of Life Science and Medical Bioscience, Waseda University Tokyo, Japan.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Chihara
authors.affiliation: Center for Biofilm Engineering, Montana State University Bozeman, MT, USA.
authors.forename: Shinya
authors.initials: S
authors.lastname: Matsumoto
authors.affiliation: Institute for Nanoscience and Nanotechnology, Waseda University Tokyo, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kagawa
authors.affiliation: Department of Life Science and Medical Bioscience, Waseda University Tokyo, Japan ; Institute for Nanoscience and Nanotechnology, Waseda University Tokyo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tsuneda
keywords: biofilm; dormancy; individual-based modeling; mathematical model; persistence