Scientific Publications
Modification of the Intestinal Microbiota with Enterobacteriaceae-specific Oligonucleotide Antimicrobials as a Novel Approach to Improve Metabolic Health
Diabetes and Obesity International Journal, 9 (2), 000291
Imbalances in the microbiota due to overgrowth of Enterobacteriaceae is associated with numerous metabolic conditionsmost
notably obesity. We describe an oligonucleotide antimicrobial, Transcription Factor Decoys (TFDs) that competitively
inhibit the Crp-FNR transcription factor highly conserved amongst Enterobacteriaceae and is critical for the regulation of
stress response and survival under anaerobic conditions. A nanoparticulate formulation delivers the TFDs to the cytoplasm of
E. coli, as visualised by confocal microscopy, rapidly reduced viable bacteria under anaerobic conditions. In vitro data showed
FNR TFD decreased up to log10 6 CFU/ml of coliforms within the Enterobacteriaceae family while other families remained
relatively undisturbed; similarly when delivered orally to wild-type mice in vivo, Enterobacteriaceae were significantly reduced
while other key bacterial populations were unaffected. This demonstrates that TFDs can be used to make precise changes to
the microbiota and has utility in testing associations between dysbiosis and disease potentially leading to the development of
microbiota targeted therapeutics to tackle obesity.
Diabetes and Obesity International Journal, 9 (2), 000291
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