MLL Lactonase Enzymes Disrupt Bacterial Quorum Sensing
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Solution Overview
Problem
Current methods to address bacterial biofilms and virulence, such as using disinfectants and antibiotics, have limited success and often lead to the selection of resistant strains, posing economic and health threats.
Innovation Solution
Development of metallo-β-lactamase-like lactonase (MLL) enzymes with specific amino acid substitutions that degrade bacterial quorum sensing signaling molecules, including genetically modified microbes and compositions for administration to animals and plants to treat infections and prevent biofilm formation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If disinfectants and antibiotics are used to address bacterial biofilms, then some level of biofilm control is achieved, but resistant strains are selected and economic/health threats increase
Solution Approach 1:
The patent converts the harmful effect of bacterial communication (quorum sensing) into a beneficial target for disruption. By designing enzymes that specifically degrade quorum sensing signaling molecules, the invention disrupts bacterial coordination without killing the bacteria, thereby preventing biofilm formation and reducing virulence while avoiding the selection of resistant strains that occurs with traditional antibiotics
Solution Approach 2:
The patent introduces an intermediary substance (quorum sensing signaling molecules) that mediates bacterial communication. By degrading these intermediary signaling molecules through enzymatic action, the invention disrupts the communication pathway between bacteria, preventing them from coordinating biofilm formation and virulence expression without directly attacking the bacteria themselves
2Reliability
If lactonases are used to degrade quorum sensing signaling molecules, then bacterial communication is disrupted, but the enzymes have been difficult to use effectively
Solution Approach 1:
The patent applies parameter changes by modifying amino acid residues in the lactonase enzyme structure. Specific substitutions at defined positions alter the enzyme's properties to improve stability, activity, or substrate specificity, making the enzyme more effective and easier to use for degrading quorum sensing signaling molecules in practical applications
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 use of MLL enzymes significantly reduces bacterial biofilms and virulence by disrupting quorum sensing communication, effectively addressing the limitations of existing treatments and providing a novel approach to managing biofilm-related issues.
Implementation Method 1
Enzymes (proteins), often referred to as lactonases, that degrade the small signaling molecules responsible for bacterial quorum sensing
Data Source
AI summary
Provided herein are lactonases. In one embodiment, the lactonases are metallo-β-lactamase-like lactonase (MLL) enzymes having altered characteristics such as altered catalytic activity and/or altered substrate specificity. Also provided are genetically modified microbes able to express a MLL enzyme, compositions that include a MLL enzyme, and methods of using a MLL enzyme.