Microbiome therapeutics to inhibit the growth of CRE and VRE

Reference number 11471

Sectors: Biotechnology, Healthcare

Industries: Therapeutics

A proposed microbiome therapeutic against CRE and VRE, comprising a synthetic microbial consortium and inhibitory metabolites.

Proposed use

The technology could form the basis of a novel microbiome therapy to inhibit CRE or VRE growth.

Problem addressed

The intestine is the primary colonisation site and reservoir for pathogens called carbapenem-resistant Enterobacteriaceae (CRE) and vancomycin-resistant Enterococcus (VRE). CRE and VRE intestinal colonisation precedes the development of other serious antibiotic-resistant infections, such as bloodstream infections or recurrent urinary tract infections. Antibiotic-mediated killing of gut microbiota members allows CRE and VRE to colonise and dominate the intestine. Antibiotics increase the concentration of nutrients available to support CRE and VRE growth, coupled with a reduction in the concentration of metabolites that can inhibit CRE and VRE growth.

Our novel approach will benefit patients by inhibiting the long-term growth of VRE and CRE, reducing the risk of developing serious infection.

Technology overview

Researchers at Imperial have identified a range of microbial metabolites that inhibit CRE and VRE growth. Figure 1 (below) shows that the growth of E.coli, K. pneumoniae and E. cloacae was inhibited through the introduction of specific microbial metabolites. The presence of these metabolites in antibiotic-treated faecal microbiota is reduced.

The proposed microbiome therapeutic consists of a synthetic microbial consortium (specific members of the gut microbiota) and these inhibitory metabolites. The introduction of inhibitory metabolites will cause an initial reduction in CRE or VRE growth. Then, the synthetic microbial consortium will colonise the intestine, outcompeting VRE and CRE for nutrients, and producing further inhibitory metabolites, resulting in long-term reduction in CRE or VRE growth.

4 graphs showing the effect of individual metabolites on the growth inhibition of certain bacteria. Conclusions described below.

a-c) CRE growth was inhibited by individual metabolites in a dose-dependent manner. Growth of E. coli, K. pneumoniae, or E. cloacae in LB supplemented with an individual metabolite at low, average, or high concentrations (mimicking stool concentrations) or unsupplemented (no metabolite control) at pH 6.5.
d) CRE growth was inhibited by a mixture of metabolites that were decreased in antibiotic-treated faecal microbiota. E. coli, K. pneumoniae, or E. cloacae were grown in LB supplemented with a metabolite mixture (mimicking average human faecal concentrations) or unsupplemented (“no metabolite” control) at pH 6, 6.5, or 7.

Benefits

  • Microbiome therapeutic approach to inhibiting long-term growth of CRE and VRE
  • Removing CRE or VRE intestinal colonization reduces the risk of serious antibiotic-resistant bacterial infection
  • Proposes wide spectrum of nutrients and metabolites important to the inhibition of CRE or VRE

Intellectual property information

UK Patent Application No. 2217266.2

Inventor

Dr Julie McDonald

Lecturer (MRC-CMBI)
Faculty of Natural Sciences, Department of Life Sciences

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Contact

Edmond Yau

Industry Partnerships and Commercialisation Executive – Faculty of Natural Sciences

Edmond joined Imperial in February 2022 as an Industry Partnerships and Commercialisation Executive. He primarily takes care of IP and licensing cases from the Faculty of Natural Sciences. Prior to joining Imperial, Edmond worked in Royal College of Art as Intellectual Property Manager who assists with queries regarding intellectual property especially patents and copyrights. Edmond has rich experience in transferring technology from tertiary institution to private sector before he moved to the UK. Edmond worked in the Hong Kong University of Science and Technology and the Chinese University of Hong Kong for more than a decade handling around several hundreds of inventions and thousands of patent applications/patents from Faculties of Engineering, Science and Medicine. He was also responsible for advising on IP strategy, patent prosecution, and the resolution of IP ownership. In addition to this, Edmond was in charge of the invention disclosure process, patent prosecution as well as licensing negotiations. He handled various types of agreements, including confidentiality, licensing, joint-ownership and royalty sharing agreements. Edmond is a patent agent by training (qualified in the People Republic of China in 2016), with his first degree in Chemical Engineering and a Master degree in Laws specialised in IP Laws from the […]

Contact Edmond

[email protected]

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