title: The spatial profiles and metabolic capabilities of microbial populations impact the growth of antibiotic-resistant mutants.
abstract: Antibiotic resistance adversely affects clinical and public health on a global scale. Using the opportunistic human pathogen Pseudomonas aeruginosa, we show that increasing the number density of bacteria, on agar containing aminoglycoside antibiotics, can non-monotonically impact the survival of antibiotic-resistant mutants. Notably, at high cell densities, mutant survival is inhibited. A wide range of bacterial species can inhibit antibiotic-resistant mutants. Inhibition results from the metabolic breakdown of amino acids, which results in alkaline by-products. The consequent increase in pH acts in conjunction with aminoglycosides to mediate inhibition. Our work raises the possibility that the manipulation of microbial population structure and nutrient environment in conjunction with existing antibiotics could provide therapeutic approaches to combat antibiotic resistance.
authors.affiliation: Department of Molecular Biosciences, University of Texas, Austin, TX 78712, USA Center for Nonlinear Dynamics and Department of Physics, University of Texas, Austin, TX 78712, USA.
authors.forename: Karishma S
authors.initials: KS
authors.lastname: Kaushik
authors.affiliation: Center for Nonlinear Dynamics and Department of Physics, University of Texas, Austin, TX 78712, USA.
authors.forename: Nalin
authors.initials: N
authors.lastname: Ratnayeke
authors.affiliation: Center for Nonlinear Dynamics and Department of Physics, University of Texas, Austin, TX 78712, USA.
authors.forename: Parag
authors.initials: P
authors.lastname: Katira
authors.affiliation: Center for Nonlinear Dynamics and Department of Physics, University of Texas, Austin, TX 78712, USA Institute of Cellular and Molecular Biology, University of Texas, Austin, TX 78712, USA gordon@chaos.utexas.edu.
authors.forename: Vernita D
authors.initials: VD
authors.lastname: Gordon
mesh_terms: D000900:Anti-Bacterial Agents / Q000378:metabolism*; D024881:Drug Resistance, Bacterial / Q000502:physiology*; D006801:Humans; D050296:Microbial Viability; D008954:Models, Biological; D009154:Mutation; D011550:Pseudomonas aeruginosa / Q000235:genetics* / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents
keywords: Pseudomonas aeruginosa; aminoglycoside; antibiotic resistance; bacterial cell density; cystic fibrosis; spatial structure of bacterial populations