Metabolite Biomarkers for Mycobacterium avium paratuberculosis Detection
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Solution Overview
Problem
Current methods for detecting Mycobacterium avium paratuberculosis, such as antibody-based tests, are inefficient, particularly at the subclinical stage, leading to challenges in accurately assessing infection status in cattle and potential links to Crohn's disease in humans, with existing tests exhibiting variable sensitivity and specificity.
Innovation Solution
A method involving the determination of specific metabolites like 2-hydroxyglutaric acid, leukotriene B4, itaconic acid, bicyclo-prostaglandin E2, N6-acetyl-L-lysine, and others, which are found to be significantly altered in MAP-infected subjects, allowing for high sensitivity and specificity in diagnosing the presence of Mycobacterium avium paratuberculosis using techniques like mass spectrometry and immunoassays.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If antibody-based ELISA tests are used for detecting MAP infections, then the diagnostic test can be performed, but the sensitivity and specificity are variable (28-94% sensitivity, 41-100% specificity) and insufficient for accurate detection at subclinical stage
Solution Approach 1:
The patent changes the detection parameter from antibody-based ELISA to metabolite-based mass spectrometry detection. Specifically, it measures metabolite levels (such as 2-hydroxyglutaric acid, itaconic acid, leukotriene B4, and other eicosanoids) in serum samples, which are significantly altered in MAP-infected cattle. This parameter change enables detection at the subclinical stage with high sensitivity and specificity, resolving the contradiction between measurement precision and reliability.
2Measurement precision
If repeat testing is performed to accurately assess MAP status, then the accuracy of herd status assessment improves, but the time consumption and cost increase significantly
Solution Approach 1:
The patent performs preliminary detection of metabolite levels in serum samples using mass spectrometry, which can identify MAP infections at the subclinical stage with high accuracy. By detecting metabolic changes that occur early in infection (before clinical symptoms appear), the method provides a single definitive test result that eliminates the need for repeat testing, thus resolving the contradiction between assessment accuracy and time loss.
3Difficulty of detecting and measuring
If current diagnostic methods are used, then the infection status can be assessed, but the detection fails to identify subclinical infections where cattle are shedding MAP but show no visible symptoms
Solution Approach 1:
The patent replaces the mechanical/chemical ELISA assay system with mass spectrometry detection. Mass spectrometry measures the actual metabolite levels in serum, providing direct information about the metabolic state of the animal. Since metabolite levels are significantly altered in MAP-infected cattle even at subclinical stages, this substitution enables detection of infections that antibody-based tests miss, resolving the contradiction between detection capability and information loss.
Data Source
AI summary
The present invention relates to a method for determining the presence of Mycobacterium avium paratuberculosis in a subject. The method comprises: (i) determining the level of one or more metabolites in a sample from the subject; and (ii) comparing the level of said one or more metabolites with the level of said one or more metabolites in a control sample to determine whether Mycobacterium aviumparatuberculosis is present in the subject. The metabolites are selected from: 2-hydroxyglutaric acid; leukotriene B4; itaconic acid; bicyclo-prostaglandin E2; N6-acetyl-L-lysine; guanidinobutanoic acid; creatine; docosahexaenoic acid; cis-10-non-adecenoic acid; creatinine; 5-hydroxyeicosapentaenoic acid, 17-hydroxy docosahexaenoic acid, palmitoleic acid; R-3-hydroxy-octade-canoic acid; 8, 11, 14-eicosatrienoic acid; nonadecanoic acid; stearic acid; eicosapentaenoic acid; 16-methylheptadecanoic acid; phytanic acid; arachidonic acid; 9,10-dihydroxy-12-octadecenoic acid, 8,11,14, 17-eicosatetraenoic acid; palmitic acid; pyruvic acid; and p-cresol.