Bacteriophage Detection of Sequestered Borrelia
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Solution Overview
Problem
Current diagnostic methods for detecting Borrelia burgdorferi sensu lato and Relapsing Fever Borrelia are plagued by low sensitivity, particularly in later stages of infection, as bacteria sequester in the nervous system, and existing methods often result in false positives or negatives, leading to misdiagnosis and inappropriate treatment.
Innovation Solution
The use of specific bacteriophages that target Borrelia species, allowing for the detection of phage presence in blood, urine, or other samples, which correlates with the presence of Borrelia, enabling accurate identification regardless of infection stage through nucleic acid or protein detection.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional diagnostic methods (culture, microscopy, antibody testing) are used to detect Borrelia, then the diagnosis can be made based on immune response or bacterial morphology, but the sensitivity is low particularly in later stages of infection when bacteria sequester in the nervous system
Solution Approach 1:
The patent uses bacteriophages as intermediary entities to detect Borrelia bacteria. The phages bind specifically to Borrelia surface structures, serving as a mediator that amplifies the detection signal. This allows indirect detection of the bacteria through their phage partners, overcoming the limitation of directly detecting sequestered bacteria in nervous system tissues.
Solution Approach 2:
The patent detects Borrelia by detecting copies of the phage-Borrelia interaction complex rather than the bacteria themselves. The phage particles serve as detectable copies or proxies for the presence of Borrelia, allowing sensitive detection even when the actual bacteria are hidden in nervous system tissues and inaccessible to conventional sampling methods.
2Productivity
If antibody-based diagnostic methods are used to detect Borrelia infection, then the immune response can be measured, but false positives and negatives occur leading to misdiagnosis and inappropriate treatment
Solution Approach 1:
The patent replaces the immunological detection mechanism (antibody-antigen interaction) with a direct viral-bacterial interaction mechanism. Instead of measuring the host's immune response which can be unreliable, the method directly detects the phage-Borrelia complex through nucleic acid or protein detection, providing more accurate and reliable diagnostic results.
Solution Approach 2:
The patent changes the detection parameter from measuring antibody concentrations (which can be variable and unreliable) to detecting phage nucleic acids or proteins (which provide a more stable and specific signal). This parameter change eliminates the false positives and negatives associated with antibody-based testing.
3Manufacturing precision
If bacterial culture methods are used to identify Borrelia, then the bacteria can be grown and characterized, but it takes up to 7 weeks and cannot differentiate between Lyme disease and Relapsing Fever bacteria
Solution Approach 1:
The patent segments the detection process into two independent parts: detecting the phage component and detecting the Borrelia component. This allows rapid identification of Borrelia presence through phage detection without requiring time-consuming bacterial culture and characterization, while maintaining the ability to differentiate between disease types through phage-specificity testing.
Solution Approach 2:
The patent performs preliminary detection of phage-Borrelia complexes before bacterial culture is completed. By detecting the phage particles that bind to Borrelia surface structures, the system can quickly identify infection presence and type without waiting for the 7-week culture period, enabling earlier treatment decisions.
4Ease of operation
If direct detection methods are used to find Borrelia in blood samples, then the bacteria can be located, but sensitivity is low particularly in later stages when bacteria migrate to the nervous system
Solution Approach 1:
The patent uses phages as intermediaries that remain in the blood and other accessible samples even when Borrelia bacteria migrate to the nervous system. The phages bind to Borrelia surface structures and are released into the bloodstream, serving as detectable markers that maintain sensitivity throughout all infection stages without requiring invasive neural tissue sampling.
Data Source
AI summary
This invention relates to methods of detecting Borrelia burgdorferi sensu lato or for detecting Borrelia associated with Relapsing Fever (RF), kits for carrying out such methods, and methods of treating Borrelia burgdorferi sensu lato or RF infections in a subject. Uses of phage specific for Borrelia are also provided.


