title: Bacterial cheating drives the population dynamics of cooperative antibiotic resistance plasmids.
abstract: Inactivation of β-lactam antibiotics by resistant bacteria is a 'cooperative' behavior that may allow sensitive bacteria to survive antibiotic treatment. However, the factors that determine the fraction of resistant cells in the bacterial population remain unclear, indicating a fundamental gap in our understanding of how antibiotic resistance evolves. Here, we experimentally track the spread of a plasmid that encodes a β-lactamase enzyme through the bacterial population. We find that independent of the initial fraction of resistant cells, the population settles to an equilibrium fraction proportional to the antibiotic concentration divided by the cell density. A simple model explains this behavior, successfully predicting a data collapse over two orders of magnitude in antibiotic concentration. This model also successfully predicts that adding a commonly used β-lactamase inhibitor will lead to the spread of resistance, highlighting the need to incorporate social dynamics into the study of antibiotic resistance.
authors.affiliation: Department of Physics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Eugene A
authors.initials: EA
authors.lastname: Yurtsev
authors.forename: Hui Xiao
authors.initials: HX
authors.lastname: Chao
authors.forename: Manoshi S
authors.initials: MS
authors.lastname: Datta
authors.forename: Tatiana
authors.initials: T
authors.lastname: Artemova
authors.forename: Jeff
authors.initials: J
authors.lastname: Gore
mesh_terms: D000667:Ampicillin / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D058491:Bacterial Load / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D022761:Gene Transfer, Horizontal / Q000187:drug effects*; D008957:Models, Genetic; D010957:Plasmids / Q000819:agonists / Q000378:metabolism*; D053038:Quorum Sensing / Q000235:genetics*; D018440:beta-Lactam Resistance / Q000187:drug effects* / Q000235:genetics; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000235:genetics / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D065093:beta-Lactamase Inhibitors; D000667:Ampicillin; D001618:beta-Lactamases
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