Broad-Spectrum Cronobacter Phage for Resistant Strain Control

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Solution Overview

Problem

Cronobacter, a highly resistant foodborne pathogen, poses a significant risk of fatal infections, particularly in powdered infant formula, with increasing drug resistance rendering conventional antibiotics ineffective, necessitating a safe and effective alternative for contamination control.

Innovation Solution

A broad-spectrum Cronobacter phage, vB_CsaM_CBT2, with a deposit number of CCTCC NO: M 2023524, is developed, capable of lysing multi-drug-resistant strains and maintaining stability across a wide pH and temperature range, used in preparations to inhibit or kill Cronobacter.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If antibiotics are used to treat Cronobacter infection, then treatment effectiveness is improved, but bacterial drug resistance increases

Engineering Contradiction:

Improvetreatment effectivenessVSAvoidbacterial drug resistance

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent converts the harmful factor of bacterial drug resistance into a benefit by selecting and utilizing phages that specifically target resistant Cronobacter strains. The phage therapy approach transforms the resistance problem into an opportunity to develop targeted biological control agents that overcome antibiotic resistance barriers.

Inventive Principle:

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

Solution Approach 2:

The patent introduces phages as an intermediary substance between the Cronobacter bacteria and the treatment system. These phages serve as biological mediators that infect and lyse Cronobacter cells, providing a mechanism for bacterial control that does not rely on conventional antibiotics and thus avoids selecting for drug resistance.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If a phage with narrow specificity is used, then safety is improved, but lysis spectrum is limited

Engineering Contradiction:

ImprovesafetyVSAvoidlysis spectrum

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent develops a phage preparation that exhibits multi-functionality by demonstrating efficacy against multiple Cronobacter species and strains. The phage vB_CsaM_CBT2 shows broad lysis spectrum including C. sakazakii, C. turicensis, C. muytjensii, and C. condimenti, making it a universal tool for controlling diverse Cronobacter contaminants in food systems.

Inventive Principle:

Principle #6Universality (Multi-functionality)

3Productivity

If phage titer is increased to improve bactericidal effect, then killing efficiency is improved, but stability across pH and temperature ranges deteriorates

Engineering Contradiction:

Improvebactericidal effectVSAvoidphage stability

Core Design Contradiction:

ProductivityVSStability of the object's composition

Solution Approach 1:

The patent employs parameter changes by formulating the phage preparation with stabilizing agents and optimizing storage conditions to maintain phage stability across varying pH (3-11) and temperature (25-60°C) ranges. This allows the preparation to retain high titer and bactericidal activity under diverse environmental conditions encountered in food processing and storage.

Inventive Principle:

Principle #35Parameter changes

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

The Cronobacter phage vB_CsaM_CBT2 effectively targets and kills four species of Cronobacter, including multi-drug-resistant strains, providing a high titer and broad-spectrum lysis with a bactericidal effect of 80.55% to 99.97% in milk powder samples, meeting safety requirements for practical applications.

Implementation Method 1

A phage is a virus that hosts a specific bacterial cell, injects its genetic materials into the host bacterium through a tail organelle, and then lyses the bacterium

Methodology Applied

Scientific EffectPhage infection and lysis:

Data Source

PatentUS20250243470A1Broad-Spectrum Phage for Efficiently Lysing Cronobacter, Bactericide, and Use

Publication Date: 2025.07.31 HEFEI UNIV OF TECH

AI summary

Disclosed is a broad-spectrum phage for efficiently lysing Cronobacter, a bactericide, and use thereof. Also provided is a Cronobacter phage vB_CsaM_CBT2, where the phage has a deposit number of CCTCC NO: M 2023524. The phage only specifically lyses Cronobacter, has a broad lysis spectrum, and can cover four species of Cronobacter (including multi-drug-resistant bacteria). The phage shows a desirable stability at a pH value of 3 to 11 and 25° C. to 70° C., and has a bactericidal effect of 80.55% to 99.97% within 12 h in a milk powder sample. Moreover, the phage does not carry any virulence and antibiotic resistance genes, and meets the safety requirements in practical applications. Therefore, the phage provides a new strategy and resource guarantee for the control of Cronobacter contamination in powdered infant formula (PIF) and its industrial chain and environment, as well as the development of bactericides.