Monoclonal Antibody Targeting EspB to Inhibit T3SS in MDR Bacteria
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Solution Overview
Problem
The emergence of multiple-drug resistant (MDR) bacterial strains poses a significant global public health concern due to their resistance to antibiotics, with existing diagnostic and therapeutic strategies being inadequate for rapid and accurate surveillance and treatment, particularly for pathogens like Escherichia coli, Salmonella, and Pseudomonas, which utilize the Type III secretion system (T3SS) for virulence.
Innovation Solution
Development of a human monoclonal antibody, mAb-B7, specifically targeting the EspB protein within the T3SS of MDR bacteria, which inhibits the injection of virulence proteins into host cells, thereby preventing bacterial survival and replication, and is designed for therapeutic and diagnostic applications.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional antibiotics are used to treat bacterial infections, then treatment is effective for antibiotic-sensitive bacteria, but treatment fails for multidrug-resistant (MDR) bacterial strains
Solution Approach 1:
The patent extracts and targets the specific virulence mechanism (T3SS) used by MDR bacteria rather than attempting to kill the bacteria directly with antibiotics. By developing monoclonal antibodies that specifically bind to and inhibit the T3SS needle protein, the treatment addresses the pathogenicity mechanism that is common across multiple MDR bacterial strains, thereby overcoming antibiotic resistance.
Solution Approach 2:
The patent changes the therapeutic approach from antibiotic-based bacterial killing to antibody-based virulence factor inhibition. This parameter change in treatment strategy allows effective intervention against MDR bacteria by targeting the T3SS system, which remains vulnerable despite bacterial resistance to conventional antibiotics.
2Reliability
If rapid and accurate surveillance and diagnosis of MDR bacteria are implemented, then treatment efficacy is improved, but diagnostic capability is currently insufficient
Solution Approach 1:
The monoclonal antibody against the T3SS needle protein serves multiple functions: it can be used as a therapeutic agent to inhibit bacterial virulence, as a diagnostic tool for detecting MDR bacteria through its specific binding, and as a research reagent for studying T3SS mechanisms. This multi-functionality addresses both treatment and diagnostic needs simultaneously.
3Adaptability or versatility
If monoclonal antibodies targeting T3SS are developed, then new therapeutic approach is provided for MDR bacteria, but existing diagnostic and therapeutic strategies are inadequate
Solution Approach 1:
The monoclonal antibody acts as an intermediary molecule that bridges the gap between the host immune system and the MDR bacteria. By binding to the T3SS needle protein, the antibody mediates inhibition of virulence factor injection into host cells, providing a therapeutic mechanism that is effective against MDR bacteria without requiring direct bacterial cell wall targeting like conventional antibiotics.
Data Source
AI summary
The invention relates to human antibodies specific for Type III secretion system (T3SS), variants and biosimilars thereof. The human antibodies of the invention are specifically directed at the EspB protein. The preset disclosure further provides compositions and uses of the disclosed antibodies in treatment and diagnosis of MDR pathogenic bacterial infections.