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Methods for Detecting Cytotoxic Amyloids Following Infection of Pulmonary Endothelial Cells by Pseudomonas aeruginosa
Published on: July 12, 2018
Targeting extracellular lectins of Pseudomonas aeruginosa with glycomimetic liposomes
Olga Metelkina1,2,3, Benedikt Huck4,5, Jonathan S O'Connor6,7
1Chemical Biology of Carbohydrates, Helmholtz Institute for Pharmaceutical Research Saarland, Helmholtz Centre for Infection Research, 66123 Saarbrücken, Germany. alexander.titz@helmholtz-hzi.de.
Abstract:
The antimicrobial resistance crisis requires novel approaches for the therapy of infections especially with Gram-negative pathogens. Pseudomonas aeruginosa is defined as priority 1 pathogen by the WHO and thus of particular interest. Its drug resistance is primarily associated with biofilm formation and essential constituents of its extracellular biofilm matrix are the two lectins, LecA and LecB. Here, we report microbial lectin-specific targeted nanovehicles based on liposomes. LecA- and LecB-targeted phospholipids were synthesized and used for the preparation of liposomes. These liposomes with varying surface ligand density were then analyzed for their competitive and direct lectin binding activity. We have further developed a microfluidic device that allowed the optical detection of the targeting process to the bacterial lectins. Our data showed that the targeted liposomes are specifically binding to their respective lectin and remain firmly attached to surfaces containing these lectins. This synthetic and biophysical study provides the basis for future application in targeted antibiotic delivery to overcome antimicrobial resistance.
Insights
Researchers developed targeted liposomes that specifically bind to bacterial lectins LecA and LecB. This innovation offers a promising strategy for delivering antibiotics to combat antimicrobial resistance in Gram-negative pathogens like Pseudomonas aeruginosa.
Area of Science:
- Biotechnology and Nanomedicine
- Microbiology and Infectious Diseases
- Drug Delivery Systems
Background:
- Antimicrobial resistance (AMR) is a global health crisis, particularly concerning Gram-negative pathogens.
- Pseudomonas aeruginosa, a WHO Priority 1 pathogen, exhibits significant drug resistance, often linked to biofilm formation.
- Bacterial lectins LecA and LecB are key components of the Pseudomonas aeruginosa biofilm matrix.
Purpose of the Study:
- To develop novel nanovehicles for targeted therapy against Pseudomonas aeruginosa.
- To investigate the potential of microbial lectin-specific liposomes for enhanced antibiotic delivery.
- To create a platform for overcoming AMR through targeted antimicrobial strategies.
Main Methods:
- Synthesis of LecA- and LecB-targeted phospholipids for liposome preparation.
- Analysis of liposome binding activity to bacterial lectins at varying surface ligand densities.
- Development of a microfluidic device for optical detection of liposome-lectin interactions.
Main Results:
- Targeted liposomes demonstrated specific binding to their respective bacterial lectins (LecA and LecB).
- Liposomes exhibited firm attachment to surfaces presenting these lectins.
- The microfluidic device successfully enabled optical detection of the targeting process.
Conclusions:
- Lectin-targeted liposomes represent a viable strategy for specific binding to Pseudomonas aeruginosa.
- This approach provides a foundation for developing targeted antibiotic delivery systems.
- The study offers a potential pathway to overcome antimicrobial resistance in challenging Gram-negative infections.

