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Publication
Two-week administration of engineered Escherichia coli establishes persistent
resistance to diet-induced obesity even without antibiotic pre-treatment.
Authors Dosoky NS, Chen Z, Guo Y, McMillan C, Flynn CR, Davies SS
Submitted By Submitted Externally on 6/24/2019
Status Published
Journal Applied microbiology and biotechnology
Year 2019
Date Published 6/1/2019
Volume : Pages Not Specified : Not Specified
PubMed Reference 31203417
Abstract Adverse alterations in the composition of the gut microbiota have been
implicated in the development of obesity and a variety of chronic diseases.
Re-engineering the gut microbiota to produce beneficial metabolites is a
potential strategy for treating these chronic diseases.
N-acyl-phosphatidylethanolamines (NAPEs) are a family of bioactive lipids with
known anti-obesity properties. Previous studies showed that administration of
Escherichia coli Nissle 1917 (EcN) engineered with Arabidopsis thaliana NAPE
synthase to produce NAPEs imparted resistance to obesity induced by a high-fat
diet that persisted after ending their administration. In prior studies, mice
were pre-treated with ampicillin prior to administering engineered EcN for
8 weeks in drinking water. If use of antibiotics and long-term administration
are required for beneficial effects, implementation of this strategy in humans
might be problematic. Studies were therefore undertaken to determine if less
onerous protocols could still impart persistent resistance and sustained NAPE
biosynthesis. Administration of engineered EcN for only 2 weeks without
pre-treatment with antibiotics sufficed to establish persistent resistance.
Sustained NAPE biosynthesis by EcN was required as antibiotic treatment after
administration of the engineered EcN markedly attenuated its effects. Finally,
heterologous expression of human phospholipase A/acyltransferase-2 (PLAAT2) in
EcN provided similar resistance to obesity as heterologous expression of A.
thaliana NAPE synthase, confirming that NAPEs are the bioactive mediator of this
resistance.





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