MccPDI Microcin Targets OmpF Porin to Kill Pathogenic E. coli

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Solution Overview

Problem

The increasing prevalence of antibiotic-resistant pathogenic bacteria, such as enterohemorrhagic E. coli, poses a challenge in treating infections effectively, as conventional antibiotics often worsen symptoms and select for resistant strains, necessitating the development of novel strategies to control these bacteria.

Innovation Solution

The use of a novel microcin, MccPDI, which is secreted via a type I secretion system and targets the OmpF protein in the outer membrane of susceptible E. coli strains, providing a proximity-dependent inhibition mechanism to kill pathogenic E. coli strains, including E. coli O157:H7 and O26, by forming pores or inhibiting protein synthesis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional antibiotics are used to treat pathogenic E. coli infections, then the infection can be treated, but antibiotic resistance develops and symptoms may worsen

Engineering Contradiction:

Improveeffectiveness of treatmentVSAvoidantibiotic resistance

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent converts the harmful effect of bacterial cell membranes into a beneficial targeting mechanism. The microcin MccPDI specifically targets and binds to the OmpF porin protein in the outer membrane of E. coli, using this structural feature as a vulnerability to deliver toxic activity directly to the cell, thereby eliminating the need for conventional antibiotics that promote resistance.

Inventive Principle:

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

Solution Approach 2:

The patent extracts and utilizes a specific protein target (OmpF porin) from the bacterial cell membrane as the basis for microcin activity. By focusing on this specific extracellular protein as the entry point and target, the microcin achieves selective toxicity without affecting human cells, thus avoiding the resistance issues associated with conventional antibiotics.

Inventive Principle:

Principle #2Taking out (Extraction)

2Productivity

If conventional antibiotics are used to control bacterial populations, then pathogenic bacteria can be eliminated, but resistant strains emerge and dominate

Engineering Contradiction:

Improvebacterial control efficiencyVSAvoidbacterial resistance adaptation

Core Design Contradiction:

ProductivityVSAdaptability or versatility

Solution Approach 1:

The patent changes the fundamental parameter of bacterial control from chemical antibiotics to a protein-based microcin mechanism. This parameter change shifts the mode of action from broad-spectrum chemical inhibition to specific protein-targeted toxicity, thereby preventing the selection pressure that drives bacterial adaptation and resistance development.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent converts the bacterial outer membrane structure, which normally serves as a protective barrier, into a vulnerability. The OmpF porin protein, essential for bacterial survival, becomes the target for microcin binding and toxic activity, thereby using the bacteria's own structural features against them without promoting resistance.

Inventive Principle:

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

3Reliability

If antibiotics are used to treat E. coli infections, then the infection is treated, but Shiga-toxin production increases and HUS risk worsens

Engineering Contradiction:

Improveinfection treatmentVSAvoidShiga-toxin production

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent converts the harmful effect of Shiga-toxin production into a beneficial targeting mechanism. The microcin MccPDI specifically targets and binds to the OmpF porin protein, which is also a receptor for Shiga-toxin. By delivering toxic activity through this same protein pathway, the microcin inhibits bacterial growth and toxin production without inducing the harmful effects associated with conventional antibiotic treatment.

Inventive Principle:

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

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

MccPDI effectively reduces the population of susceptible E. coli strains by greater than 5 logs, demonstrating its potential as a therapeutic and prophylactic agent against pathogenic E. coli, reducing the reliance on antibiotics and their associated resistance issues.

Implementation Method 1

The microcin MccPDI has been shown to kill susceptible E. coli strains by forming pores or inhibiting protein synthesis

Methodology Applied

Scientific EffectPore formation:

Implementation Method 2

The microcin MccPDI has been shown to kill susceptible E. coli strains by forming pores or inhibiting protein synthesis

Methodology Applied

Scientific EffectProtein synthesis inhibition:

Data Source

PatentUS10220071B2Microcin and uses thereof

Publication Date: 2019.03.05 WASHINGTON STATE UNIVERSITY

AI summary

Microcin MccPDI and bacteria harboring the mcpM gene which encodes MccPDI limit growth of and/or kill pathogenic bacteria such as pathogenic Escherichia coli (E. coli) and/or Shigella bacteria via proximity-dependent inhibition (PDI).