Bacteriophage Strains Against Proteus Mirabilis Biofilms
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current treatments for urinary tract infections caused by Proteus mirabilis, especially those involving biofilm formation, are ineffective due to the emergence of multidrug-resistant strains, and there is a lack of effective methods for preventing and eradicating biofilms on urinary catheters.
Innovation Solution
Development of specific bacteriophage strains, such as 72APm5211, 39APmC32, and 65APm2833, which are deposited with the Polish Collection of Microorganisms, that can target and destroy biofilms formed by Proteus mirabilis, including multidrug-resistant strains, either alone or in combination with antibiotics.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional antibiotics are used to treat Proteus mirabilis infections, then initial treatment effectiveness is achieved, but multidrug-resistant strains emerge rendering treatments ineffective
Solution Approach 1:
The patent employs bacteriophages as intermediary agents that specifically target and infect Proteus mirabilis bacteria. These phages serve as a mediator between the treatment goal and the resistant bacteria, utilizing their natural infectivity to destroy bacterial cells without relying on antibiotic mechanisms that have become ineffective due to resistance development.
Solution Approach 2:
The invention changes the fundamental parameter of treatment mechanism from chemical antibiotic action to biological phage infection. By switching from antibiotics that target bacterial metabolism to bacteriophages that replicate within and lyse bacterial cells, the treatment overcomes resistance mechanisms that specifically counter antibiotic actions.
2Adaptability or versatility
If bacteriophage strains are used to target Proteus mirabilis, then specificity against target bacteria is improved, but the complexity of identifying effective strains increases
Solution Approach 1:
The patent performs preliminary screening and characterization of bacteriophage strains against multiple Proteus mirabilis strains before clinical application. By pre-identifying phages with broad efficacy against different bacterial strains and pre-characterizing their properties, the complex identification process is simplified and standardized for future use.
Solution Approach 2:
The invention identifies bacteriophage strains that can effectively infect multiple Proteus mirabilis strains with different resistance profiles. This universal phage activity reduces the need for strain-specific matching and simplifies the treatment approach while maintaining high specificity against the target bacterial species.
3Reliability
If bacteriophages are used to destroy bacterial biofilms, then biofilm eradication is achieved, but the time required for complete destruction increases
Solution Approach 1:
The patent combines bacteriophage therapy with antibiotic treatment in a synergistic approach. The bacteriophages penetrate and disrupt the biofilm matrix while antibiotics act on the bacterial cells, particularly those exposed during phage-mediated biofilm disruption. This combination achieves complete biofilm eradication faster than either treatment alone.
Solution Approach 2:
The invention utilizes the dynamic replication and lysis cycle of bacteriophages within the biofilm structure. As phages replicate and lyse bacterial cells, they create openings and disrupt the biofilm architecture dynamically, allowing progressive penetration and destruction of deeper biofilm layers over time rather than requiring static, prolonged exposure.
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
These bacteriophage strains effectively inhibit the growth of Proteus mirabilis and destroy mature biofilms, offering a promising solution for treating and preventing urinary tract infections associated with urinary catheters by reducing biofilm formation and enhancing the efficacy of antibiotic treatments.
Implementation Method 1
Bacteriophages are viruses possessing a natural ability to destroy bacteria... virulent phages, which, as a result of the process of propagation in bacteria, lead to their destruction... Enzymes produced by phages responsible for the degradation of the bacterial cell wall or capsule
Implementation Method 2
depolymerases, which degrade capsular polysaccharides or exopolysaccharides (EPS), which are the main components of the bacterial biofilm matrix... polysaccharide depolymerases have been detected in various phages
Data Source
Figure 1
Figure 2
Figure 3A~3C
AI summary
The invention covers new bacteriophage strains specific against bacteria belonging to the species Proteus mirabilis, deposited with the Polish Collection of Microorganisms (PCM) under the access numbers: F/00084 (72APm5211), F/00085 (39APmC32), F/00086 (65APm2833), for use for use in the prophylaxis and therapy. In accordance with the invention the above mentioned bacteriophage strains, in form of complete particles of the single bacteriophage strain, in form of bacteriophage lysates, optionally in form of purified bacteriophage proteins, in particular lytic enzymes that degrade the bacterial cell wall and enzymes that decompose bacterial extracellular polysaccharides, are intended for use in therapy as anti-bacterial agents, in particular against bacteria of the species Proteus mirabilis, especially the drug- and multidrug- resistant strains of the species, advantageously in urinary tract infections. In accordance with the invention the above mentioned bacteriophage strains, in form of a coctail comprising two or more active bacteriophages, in form of lysates of two or more active bacteriophages, optionally in form of purified bacteriophage proteins of two or more active bacteriophages, especially lytic enzymes that degrade the bacterial cell wall and enzymes that decompose bacterial extracellular polysaccharides, are intended for use in therapy as anti-bacterial agents, in particular against bacteria of the species Proteus mirabilis, especially the drug- and multidrug-resistant strains of the species, advantageously in urinary tract infections. The manufactured preparations or compositions are in gel or liquid form and are intended for use in combination or in composition with other anti-bacterial agent, or with other medicaments, wherein the liquid form may be used spray, compresses, rinse/wash liquid preparation or wet compresses.