Recombinant Phage Detection of Antibiotic Resistance

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Solution Overview

Problem

Current methods for detecting antibiotic resistance in microorganisms are time-consuming, technically demanding, and lack sufficient sensitivity, requiring isolation and culturing of microorganisms, which delays treatment and increases the risk of nosocomial infections.

Innovation Solution

A method using genetically modified infectious agents, such as recombinant phages, that contact a sample with an antibiotic and an indicator gene, allowing for the detection of antibiotic resistance without prior isolation of the microorganism, utilizing the production of an indicator protein product to determine resistance.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If current methods (immunoassays, molecular-based assays, culturing) are used for antibiotic resistance detection, then detection accuracy can be achieved, but the detection time is extended to 24-48 hours and the process becomes technically demanding

Engineering Contradiction:
Improvedetection accuracyVSAvoiddetection time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent extracts the detection function from complex culturing and isolation procedures by using phage particles that can directly infect and replicate within microorganisms in the sample. The indicator gene embedded in the phage allows direct detection of antibiotic resistance without requiring traditional culturing steps, thereby reducing detection time while maintaining accuracy

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent introduces phage particles as an intermediary between the sample and the detection system. These phage particles carry indicator genes and can infect target microorganisms, serving as a bridge that enables rapid detection of antibiotic resistance by translating biological interaction into a detectable signal without requiring lengthy culturing processes

Inventive Principle:
Principle #24Intermediary (Mediator)

2Measurement precision

If isolation and culturing of microorganisms is performed prior to detection, then detection specificity is improved, but the time-to-results is increased and the process becomes more complex

Engineering Contradiction:
Improvedetection specificityVSAvoidprocess complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent removes the isolation and culturing steps from the detection process by using phage particles that can specifically infect target microorganisms directly in the sample. The specificity is maintained through the natural host-range limitations of the phage, eliminating the need for complex isolation procedures

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The phage particles perform the function of both specific recognition and amplification themselves through their natural infection cycle. The indicator gene within the phage automatically produces a detectable signal when the phage infects the target microorganism, eliminating the need for additional detection reagents or complex procedural steps

Inventive Principle:
Principle #25Self-service

3Measurement precision

If samples with low levels of microorganisms are tested using current methods, then detection sensitivity must be increased, but the detection time is extended and technical demands increase

Engineering Contradiction:
Improvedetection sensitivityVSAvoidtime-to-results
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent incorporates the indicator gene within the phage particle itself, preparing the detection mechanism in advance. When the phage infects the target microorganism, the indicator gene is already positioned to immediately produce a detectable signal, enabling rapid detection of low-level microorganisms without requiring enrichment or extended incubation periods

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The phage particle serves as an amplifying intermediary that can detect single or low-number target microorganisms. The infection cycle of the phage naturally amplifies the signal through replication and indicator gene expression, enabling high sensitivity detection without requiring pre-enrichment of the sample

Inventive Principle:
Principle #24Intermediary (Mediator)

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

Enables rapid and sensitive detection of antibiotic resistance in microorganisms, potentially within 5 hours, without the need for culturing, allowing for timely and effective antibiotic treatment and prevention of infection spread.

Implementation Method 1

the infectious agent infects the microorganism and replicates within the microorganism to produce progeny infectious agents

Methodology Applied
Scientific EffectViral replication:

Implementation Method 2

the indicator gene encodes an indicator protein product, and detecting a signal produced by an indicator protein product

Methodology Applied
Scientific EffectGene expression:

Implementation Method 3

the indicator gene encodes an indicator protein product that generates an intrinsic signal or an enzyme that generates signal upon reaction with substrate

Methodology Applied
Scientific EffectProtein signal generation:

Data Source

PatentUS20240401105A1Methods and Systems for Detection of Antibiotic Resistance
Publication Date: 2024.12.05 LABORATORY CORPORATION OF AMERICA HOLDINGS INC
  • US20240401105A1 patent drawing

AI summary

Disclosed herein are methods and systems for rapid detection of antibiotic resistance of a microorganism in a sample. A modified recombinant phage is also disclosed which comprises an indicator gene in the late gene region. The specificity of infectious agents allows a specific microorganism to be targeted, and an indicator signal may be amplified to optimize assay sensitivity.