Medium chain unsaturated fatty acid ethyl esters inhibit persister formation of Escherichia coli via antitoxin HipB
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 form...
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Published in | Applied microbiology and biotechnology Vol. 102; no. 19; pp. 8511 - 8524 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
Berlin/Heidelberg
Springer Berlin Heidelberg
01.10.2018
Springer Springer Nature B.V |
Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0175-7598 1432-0614 |
DOI: | 10.1007/s00253-018-9271-3 |