The fatty acid signaling molecule cis-2-decenoic acid increases metabolic activity and reverts persister cells to an antimicrobial-susceptible state

Appl Environ Microbiol. 2014 Nov;80(22):6976-91. doi: 10.1128/AEM.01576-14. Epub 2014 Sep 5.


Persister cells, which are tolerant to antimicrobials, contribute to biofilm recalcitrance to therapeutic agents. In turn, the ability to kill persister cells is believed to significantly improve efforts in eradicating biofilm-related, chronic infections. While much research has focused on elucidating the mechanism(s) by which persister cells form, little is known about the mechanism or factors that enable persister cells to revert to an active and susceptible state. Here, we demonstrate that cis-2-decenoic acid (cis-DA), a fatty acid signaling molecule, is able to change the status of Pseudomonas aeruginosa and Escherichia coli persister cells from a dormant to a metabolically active state without an increase in cell number. This cell awakening is supported by an increase of the persister cells' respiratory activity together with changes in protein abundance and increases of the transcript expression levels of several metabolic markers, including acpP, 16S rRNA, atpH, and ppx. Given that most antimicrobials target actively growing cells, we also explored the effect of cis-DA on enhancing antibiotic efficacy in killing persister cells due to their inability to keep a persister cell state. Compared to antimicrobial treatment alone, combinational treatments of persister cell subpopulations with antimicrobials and cis-DA resulted in a significantly greater decrease in cell viability. In addition, the presence of cis-DA led to a decrease in the number of persister cells isolated. We thus demonstrate the ability of a fatty acid signaling molecule to revert bacterial cells from a tolerant phenotype to a metabolically active, antimicrobial-sensitive state.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Drug Resistance, Bacterial
  • Escherichia coli / drug effects*
  • Escherichia coli / growth & development
  • Escherichia coli / metabolism*
  • Fatty Acids, Monounsaturated / chemistry
  • Fatty Acids, Monounsaturated / metabolism*
  • Isomerism
  • Microbial Sensitivity Tests
  • Pseudomonas aeruginosa / drug effects*
  • Pseudomonas aeruginosa / growth & development
  • Pseudomonas aeruginosa / metabolism
  • Signal Transduction / drug effects


  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Fatty Acids, Monounsaturated
  • 2-decenoic acid