title: In Silico Evaluation of the Impacts of Quorum Sensing Inhibition (QSI) on Strain Competition and Development of QSI Resistance.
abstract: As understanding of bacterial regulatory systems and pathogenesis continues to increase, QSI has been a major focus of research. However, recent studies have shown that mechanisms of resistance to quorum sensing (QS) inhibitors (QSIs) exist, calling into question their clinical value. We propose a computational framework that considers bacteria genotypes relative to QS genes and QS-regulated products including private, quasi-public, and public goods according to their impacts on bacterial fitness. Our results show (1) QSI resistance spreads when QS positively regulates the expression of private or quasi-public goods. (2) Resistance to drugs targeting secreted compounds downstream of QS for a mix of private, public, and quasi-public goods also spreads. (3) Changing the micro-environment during treatment with QSIs may decrease the spread of resistance. At fundamental-level, our simulation framework allows us to directly quantify cell-cell interactions and biofilm dynamics. Practically, the model provides a valuable tool for the study of QSI-based therapies, and the simulations reveal experimental paths that may guide QSI-based therapies in a manner that avoids or decreases the spread of QSI resistance.
authors.affiliation: Electrical and Computer Engineering, Carnegie Mellon University, Pittsburgh, PA, USA.
authors.forename: Guopeng
authors.initials: G
authors.lastname: Wei
authors.affiliation: Electrical and Computer Engineering, Carnegie Mellon University, Pittsburgh, PA, USA.
authors.forename: Chieh
authors.initials: C
authors.lastname: Lo
authors.affiliation: Electrical and Computer Engineering, Carnegie Mellon University, Pittsburgh, PA, USA.
authors.forename: Connor
authors.initials: C
authors.lastname: Walsh
authors.affiliation: Biological Sciences, Carnegie Mellon University, Pittsburgh, PA, USA.
authors.forename: N Luisa
authors.initials: NL
authors.lastname: Hiller
authors.affiliation: Electrical and Computer Engineering, Carnegie Mellon University, Pittsburgh, PA, USA.
authors.forename: Radu
authors.initials: R
authors.lastname: Marculescu