Probiotic E. Coli Strains for Gut Decolonization of MDR Enterobacteria

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Solution Overview

Problem

Current treatments for decolonizing multi-drug resistant Enterobacteriaceae, such as E. coli and Klebsiella pneumoniae, from the gut are ineffective and can exacerbate resistance development, while existing probiotics do not effectively displace these pathogens, and fecal microbiota transplantation poses safety risks.

Innovation Solution

Utilizing specific strains of E. coli, particularly in combination with Klebsiella michiganensis and/or Klebsiella oxytoca, to outcompete and decolonize pathogenic and antibiotic-resistant Enterobacteriaceae by establishing colonization resistance in the gut.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If antibiotic treatments are used to decolonize multi-drug resistant Enterobacteriaceae, then pathogen clearance may be achieved, but antibiotic resistance development is exacerbated and microbiota disruption occurs

Engineering Contradiction:

Improvepathogen clearance efficacyVSAvoidantibiotic resistance development

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent utilizes commensal E. coli strains that naturally compete with pathogenic Enterobacteriaceae for gut colonization. Instead of using antibiotics that kill both pathogens and beneficial bacteria (causing resistance), the invention employs probiotic E. coli strains to establish colonization resistance through competitive exclusion, converting the potential harm of pathogen presence into a beneficial protective effect against future pathogen colonization

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

Solution Approach 2:

The patent introduces commensal E. coli strains as intermediary organisms that mediate between the host gut environment and pathogenic Enterobacteriaceae. These intermediary bacteria establish themselves in the gut ecosystem and prevent pathogen colonization through competition for nutrients and attachment sites, without directly contacting or killing the pathogens, thereby avoiding selection for antibiotic resistance

Inventive Principle:

Principle #24Intermediary (Mediator)

2Stability of the object's composition

If existing probiotics are used to displace pathogenic bacteria, then gut colonization may be maintained, but effective displacement of multi-drug resistant pathogens is not achieved

Engineering Contradiction:

Improvegut colonization stabilityVSAvoidpathogen displacement efficacy

Core Design Contradiction:

Stability of the object's compositionVSReliability

Solution Approach 1:

The patent identifies specific local qualities of certain commensal E. coli strains (such as adherence properties, metabolic capabilities, and competitive exclusion mechanisms) that enable them to effectively displace pathogenic Enterobacteriaceae. Rather than using generic probiotics, the invention selects strains with specific local adaptations that give them competitive advantage in the gut environment against multidrug-resistant pathogens

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent employs commensal E. coli strains with modified or optimized parameters such as enhanced adherence to gut epithelium, improved metabolic efficiency for competing with pathogens, and adjusted growth rates. These parameter changes in the probiotic strains enable them to effectively outcompete and displace multidrug-resistant pathogens while maintaining stable gut colonization

Inventive Principle:

Principle #35Parameter changes

3Adaptability or versatility

If fecal microbiota transplantation is performed to restore gut flora, then microbiota diversity may be restored, but safety risks from pathogen transmission increase

Engineering Contradiction:

Improvemicrobiota restoration capabilityVSAvoidpathogen transmission risk

Core Design Contradiction:

Adaptability or versatilityVSObject-affected harmful factors

Solution Approach 1:

The patent extracts and isolates specific beneficial commensal E. coli strains from the complex fecal microbiota, separating them from potential pathogens and harmful organisms. Instead of transplanting entire fecal material with all its microbial complexity, the invention extracts only the specific probiotic strains that have proven effective against multidrug-resistant pathogens, thereby restoring microbiota function without pathogen transmission risk

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent uses cultured commensal E. coli strains as a controlled copy or substitute for the natural fecal microbiota. Rather than directly transplanting complex fecal material, the invention grows specific beneficial strains in controlled laboratory conditions and administers them in purified form, achieving microbiota restoration effects without the safety risks associated with unprocessed fecal transplantation

Inventive Principle:

Principle #26Copying

Data Source

PatentEP4663196A1Decolonization of pathogenic enterobacteria, such as e. coli and/or klebsiella pneumoniae, from the gut using strains of e. coli

Publication Date: 2025.12.17 HELMHOLTZ ZENTRUM FUER INFEKTIONSFORSCHUNG GMBH

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AI summary

The present invention relates to probiotic bacteria of the species E. coli, in particular in combination with bacteria of the species Klebsiella oxytoca, that are used for a decolonization of pathogenic and/or multi drug resistant (MDR) Enterobacteria, such as pathogenic E. coli and/or Klebsiella pneumoniae (K. pneumoniae), Enterococci and/or Acinetobacter, from the gut of a subject. The decolonization can both be therapeutic, i.e. after colonization of the gut by the pathogenic and/or multi-resistant pathogen(s), or as a preventive measure before a re-colonization of the gut, as required after antibiotic treatment or treatment-induced dysbiosis.