Bacteriophage K Mutant for MRSA Treatment

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Solution Overview

Problem

The widespread use of antibiotics has led to an increase in antibiotic-resistant bacterial strains, particularly Methicillin-resistant Staphylococcus aureus (MRSA), which are difficult to treat with conventional antibiotics, and there is a need for an effective alternative to prevent bacterial transmission, especially in hospitals and sensitive areas like the nasal cavity.

Innovation Solution

A Staphylococcus bacteriophage K mutant with specific point mutations (C18554T, G40894A, G78197A, G99388C, G102111A, T103720C, C105975T, and A109329G) is developed, which provides broader antimicrobial action and can be used in a pharmaceutical composition for topical application to treat bacterial infections, including MRSA.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional antibiotics are used to treat bacterial infections, then initial treatment effectiveness is high, but bacterial resistance develops leading to treatment failure

Engineering Contradiction:
Improvetreatment effectivenessVSAvoidbacterial resistance
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent applies parameter changes by modifying the bacteriophage genome through specific point mutations (C18554T, G40894A, G78197A, G99388C, G102111A, T103720C, C105975T, and A109329G) to alter the phage's host range and lysogenic conversion properties, enabling it to effectively target antibiotic-resistant bacteria without being affected by bacterial resistance mechanisms

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent uses bacteriophage K*710 as an intermediary agent between the treatment goal and the resistant bacteria. The phage acts as a biological mediator that specifically infects and eliminates MRSA and other antibiotic-resistant strains through lysogenic conversion, bypassing the antibiotic resistance problem entirely

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If bacteriophage therapy is used to treat antibiotic-resistant bacteria, then treatment effectiveness against resistant strains improves, but the complexity of phage selection and application increases

Engineering Contradiction:
Improveeffectiveness against resistant strainsVSAvoidphage selection and application complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent achieves universality by developing a bacteriophage K*710 mutant that can infect multiple antibiotic-resistant bacterial strains including MRSA, MSSA, and other Staphylococcus species. The phage's broad host range and ability to induce lysogenic conversion make it a universal treatment agent for Gram-positive bacterial infections, eliminating the need for complex phage matching procedures

Inventive Principle:
Principle #6Universality (Multi-functionality)

3Reliability

If alcoholic hand-washes are used to prevent MRSA transmission, then hand hygiene effectiveness is high, but they are unsuitable for use on sensitive areas like nasal cavity and broken skin

Engineering Contradiction:
Improvehand hygiene effectivenessVSAvoidsuitability for sensitive areas
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent applies parameter changes by transitioning from chemical disinfection (alcohol) to biological disinfection (bacteriophage). The bacteriophage K*710 maintains antimicrobial effectiveness while changing the mode of action to be non-irritating and suitable for sensitive areas including nasal cavity, oral cavity, and broken skin, thus expanding the applicability parameter

Inventive Principle:
Principle #35Parameter changes

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 bacteriophage mutant effectively targets and eliminates a wider range of bacterial strains, including MRSA, offering a viable alternative to antibiotics and preventing bacterial transmission by being applied topically to infected surfaces and mucosal areas.

Implementation Method 1

In the case of obligate lytic phages, the injected viral DNA/RNA goes on to direct the production of bacteriophage progeny using the intracellular mechanisms of the host cell. The host cell is killed by lysis at the end of the cell cycle.

Methodology Applied
Scientific EffectLytic cycle:

Implementation Method 2

Most bacteriophages have structures, such as tail fibers, which enable them to bind to specific molecules on the surface of their target bacteria.

Methodology Applied
Scientific EffectSpecific binding:

Implementation Method 3

Viral DNA, usually encased within the bacteriophage head, or RNA in some bacteriophages, is then injected, usually through the tail, into the host cell.

Methodology Applied
Scientific EffectDNA injection:

Data Source

PatentEP2776559B1Novel bacteriophages
Publication Date: 2019.06.05 ARMATA PHARMACEUTICALS INC
  • EP2776559B1 patent drawingFigure 1
  • EP2776559B1 patent drawingFigure 2
  • EP2776559B1 patent drawingFigure 2

AI summary

The present invention provides a bacteriophage with effective antibacterial activity against Staphylococcus strains and in particular MRSA. There is also provided a pharmaceutical composition comprising said bacteriophage and a method of treating a bacterial infection using a composition comprising said bacteriophage.