Peter Fritz Müller

Abstract

Intracellular bacteria, such as Mycobacterium tuberculosisand Listeria monocytogenes, pose a tremendous threat to the human population. Not only can those pathogens hide from the immune system within cells, but also developed resistances against antibiotics during the past decades. This will lead to severe and hardly treatable infections in near future.

Bearer of hope in fighting even antibiotic resistance bacteria are bacteriopages (phages) - specializes viruses that can eliminate single bacterial species highly specifically. To efficiently transport phages to intracellular pathogens we developed liposomal delivery strategies to overcome the membrane of infected cells [1,2]. 

Using special encapsulation techniques, e.g. PVA swelling, and creating an inverted emulsion, we are able to generate unilamellar vesicles containing functional phages. Furthermore, we utilize the special characteristics of certain lipids to deliver the cargo into different cellular components, such as the cytosol or phagosomal vesicles - typical harbours of many intracellular bacterial pathogens. With negatively charged lipids we create constructs which can be taken up very efficiently. In combination with pH-sensitive lipids we are able to release the cargo by disintegration of the liposomes within the cells endosome. Another strategy are vesicles containing high concentrations of cationic and cone shaped lipids, leading to increased membrane tension and facilitated fusion with the plasma membrane of the cell. 

Our goal is to provide lipid-based therapeutic tools as a well-tolerated alternative to antibiotics. With our strategies we will be able to ensure the delivery of bacteriophages into different compartments of infected cells and eliminate specific bacterial pathogens.

Methods

Artificial membrane systems; bacteriophage production, purification, and encapsulation; infectious work; fluorescence microscopy

References

[1] Nieth, A; Verseux, C; Barnert, S; Süss, R; Römer, W (2015) A first step toward liposome-mediated intracellular bacteriophage therapy. Expert Opi. Drug Deliv. 12(9):1411-24

[2] Nieth, A; Verseux, C; Römer, W (2014) Dressing Up Bacteriophage Therapy for the Battle Against Antibitic-Resistant Intracellular Bacteria. Springer Sci. Rev. 1(1):1-11