Bacterial cheating drives the population dynamics of cooperative antibiotic resistance plasmids

Mol Syst Biol. 2013 Aug 6:9:683. doi: 10.1038/msb.2013.39.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Ampicillin / pharmacology
  • Anti-Bacterial Agents / pharmacology
  • Bacterial Load / drug effects
  • Escherichia coli / drug effects*
  • Escherichia coli / enzymology
  • Escherichia coli / genetics
  • Gene Transfer, Horizontal / drug effects*
  • Models, Genetic
  • Plasmids / agonists
  • Plasmids / metabolism*
  • Quorum Sensing / genetics*
  • beta-Lactam Resistance / drug effects*
  • beta-Lactam Resistance / genetics
  • beta-Lactamase Inhibitors
  • beta-Lactamases / genetics
  • beta-Lactamases / metabolism

Substances

  • Anti-Bacterial Agents
  • beta-Lactamase Inhibitors
  • Ampicillin
  • beta-Lactamases