Iron-Chelation Induced Polypeptides for Staphylococcus Infection Control

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Solution Overview

Problem

The emergence of antibiotic-resistant Staphylococcus species, such as MRSA, poses a significant challenge in treating staphylococcal infections, as existing vaccines and treatments lack broad protection and are ineffective in immunocompromised individuals and against diverse staphylococcal strains.

Innovation Solution

Development of compositions comprising isolated polypeptides with specific molecular weights and amino acid sequences, which are expressed by Staphylococcus aureus under iron chelation, and the use of antibodies that specifically bind these polypeptides to treat and prevent Staphylococcus infections.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If antibiotics are used to treat staphylococcal infections, then bacterial infections can be eliminated, but antibiotic resistance develops making treatment difficult

Engineering Contradiction:
Improveeffectiveness of treatmentVSAvoidantibiotic resistance
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent converts the harmful effect of antibiotic selection pressure into a beneficial outcome by using the iron-chelation condition to selectively induce expression of specific virulence-associated polypeptides. This creates a vulnerability in the bacteria that can be targeted by vaccines, turning the bacteria's own virulence mechanisms against them.

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

Solution Approach 2:

The patent introduces an intermediary approach by using iron chelation as a conditional trigger to express specific polypeptides, rather than directly targeting the bacteria with antibiotics. This intermediary mechanism allows for selective targeting of virulence factors while sparing normal bacterial functions.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If existing vaccines are used, then some protection is provided, but broad protection against diverse staphylococcal strains is lacking

Engineering Contradiction:
Improvevaccine protectionVSAvoidcross-protection against diverse strains
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent achieves universality by targeting polypeptides that are commonly expressed across diverse staphylococcal strains under iron-chelation conditions. The composition includes multiple polypeptides with different molecular weights that collectively provide broad-spectrum protection against various strains including MRSA, MSSA, and other staphylococcal species.

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

Solution Approach 2:

The patent uses parameter changes by exploiting the iron-chelation condition to induce expression of specific polypeptides. By changing the environmental parameter (iron availability), the bacteria express virulence-associated polypeptides that become targets for vaccine-induced immunity, providing protection that adapts to different strain variations.

Inventive Principle:
Principle #35Parameter changes

3Reliability

If traditional treatments are used, then immunocompetent individuals may be helped, but immunocompromised individuals receive no benefit

Engineering Contradiction:
Improvetreatment effectivenessVSAvoidefficacy in immunocompromised individuals
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent applies preliminary action by providing passive immunity through administered antibodies that bind to iron-chelation-induced polypeptides. This pre-established immune protection works immediately upon administration, bypassing the need for the patient's immune system to mount a response, thereby benefiting immunocompromised individuals who cannot generate their own immune response.

Inventive Principle:
Principle #10Preliminary action

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 compositions effectively protect against Staphylococcus aureus infections by neutralizing toxins and reducing colonization, offering a potential solution for treating and preventing staphylococcal infections, especially in immunocompromised individuals and against antibiotic-resistant strains.

Implementation Method 1

The polypeptides are isolatable from a Staphylococcus aureus when incubated in media including an iron chelator and not isolatable when grown in the media without the iron chelator

Methodology Applied
Scientific EffectIron chelation:

Implementation Method 2

the use of antibodies that specifically bind these polypeptides to treat and prevent Staphylococcus infections

Methodology Applied
Scientific EffectAntibody-antigen binding:

Data Source

PatentUS9932373B2Polypeptides and immunizing compositions containing gram positive polypeptides and methods of use
Publication Date: 2018.04.03 VAXXINOVA US INC
  • US9932373B2 patent drawing
  • US9932373B2 patent drawing
  • US9932373B2 patent drawing

AI summary

The present invention provides isolated polypeptides isolatable from a Staphylococcus spp. Also provided by the present invention are compositions that include one or more of the polypeptides, and methods for making and methods for using the polypeptides.