Applied Microbiology and Biotechnology

, Volume 102, Issue 19, pp 8511–8524 | Cite as

Medium chain unsaturated fatty acid ethyl esters inhibit persister formation of Escherichia coli via antitoxin HipB

  • Mengya Wang
  • Kuili Fang
  • Sung Min Choi Hong
  • Inwha Kim
  • Ik-Soon Jang
  • Seok Hoon HongEmail author
Applied microbial and cell physiology


Persisters represent a small bacterial population that is dormant and that survives under antibiotic treatment without experiencing genetic adaptation. Persisters are also considered one of the major reasons for recalcitrant chronic bacterial infections. Although several mechanisms of persister formation have been proposed, it is not clear how cells enter the dormant state in the presence of antibiotics or how persister cell formation can be effectively controlled. A fatty acid compound, cis-2-decenoic acid, was reported to decrease persister formation as well as revert the dormant cells to a metabolically active state. We reasoned that some fatty acid compounds may be effective in controlling bacterial persistence because they are known to benefit host immune systems. This study investigated persister cell formation by pathogens that were exposed to nine fatty acid compounds during antibiotic treatment. We found that three medium chain unsaturated fatty acid ethyl esters (ethyl trans-2-decenoate, ethyl trans-2-octenoate, and ethyl cis-4-decenoate) decreased the level of Escherichia coli persister formation up to 110-fold when cells were exposed to ciprofloxacin or ampicillin antibiotics. RNA sequencing analysis and gene deletion persister studies elucidated that these fatty acids inhibit bacterial persistence by regulating antitoxin HipB. A similar persister cell reduction was observed for pathogenic E. coli EDL933, Pseudomonas aeruginosa PAO1, and Serratia marcescens ICU2-4 strains. This study demonstrates that fatty acid ethyl esters can be used to disrupt bacterial dormancy to combat persistent infectious diseases.


Persister cells Fatty acid ethyl esters Ethyl trans-2-decenoate Ethyl trans-2-octenoate Ethyl cis-4-decenoate 



We thank Dr. Olga Zaborina at the University of Chicago for providing a S. marcescens clinical isolate and Dr. Kevin Kunstman at the Research Resources Center at the University of Illinois at Chicago for helping with RNA sequencing.


This study was funded by the Educational and Research Initiative Fund at Illinois Institute of Technology.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Supplementary material

253_2018_9271_MOESM1_ESM.pdf (160 kb)
ESM 1 (PDF 159 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Chemical and Biological EngineeringIllinois Institute of TechnologyChicagoUSA
  2. 2.Division of Bioconvergence AnalysisKorea Basic Science InstituteDaejeonRepublic of Korea

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