A Novel Mechanism for Disrupting Biofilms and Combating Antimicrobial Resistance

This invention reveals new mechanistic details on how the antimicrobial peptide PLG0206 disrupts bacterial biofilms and the rare, low-probability ways bacteria develop resistance to it. It provides a powerful new approach for developing effective treatments against persistent bacterial infections by targeting vulnerabilities in biofilm integrity and showing a unique resistance mechanism.

Description

The invention uses a solid-state NMR (ssNMR) to analyze native biofilms of Staphylococcus aureus, a gram-positive bacterium, without requiring extraction or purification. The studies revealed that PLG0206 primarily targets and reduces levels of wall teichoic acid (WTA) within the biofilm, a finding confirmed by 2D ssNMR. The peptide's effect is selective; it does not interact with extracellular DNA (eDNA), despite eDNA's similar negative charge, showing that binding isn't purely electrostatic. This binding action disrupts the structural integrity of the biofilm, a crucial step in combating chronic infections. It was found that resistance development in gram-positive organisms is a low-probability event that requires a double mutation. This novel resistance mechanism is based on a change in the bacteria's membrane potential, which is linked to a mutation in a potassium transport pump. The difficulty in developing resistance makes this technology highly promising for future antimicrobial strategies.

Applications

- Treating persistent bacterial infections associated with biofilms.
- Developing new antimicrobial peptides with a low risk of resistance.
- Improving medical devices by creating coatings that prevent biofilm formation.
- Formulating novel therapies for gram-positive bacterial infections, including S. aureus and S. epidermidis.
- Advancing research tools for studying biofilms in their native state using ssNMR.

Advantages

- Disrupts Biofilms
- Selective Targeting
- Difficult Resistance Development
- Effective on Multiple Species
- Potential for New Drug Development

Invention Readiness

This intellectual property is at the proof of concept stage, and both in vitro and in vivo data have been generated to support its claims. The data validates the mechanism of action, showing the compound disrupts biofilms by targeting wall teichoic acid, and confirms the difficulty of resistance development. Further refinement of the data is needed, but significant additional data has already been collected.

IP Status

Patent Pending