Für den Inhalt der Angaben zeichnet die Projektleitung verantwortlich.
Dieses von der Gebert Rüf Stiftung geförderte Projekt wird von folgenden weiteren Projektpartnern mitgetragen: LASCCO SA, Geneva, Biomedical Technology Development
Project no: GRS-073/14
Amount of funding: CHF 293'000
Duration: 07.2015 - 07.2019
Area of activity: Pilotprojekte, 1998 - 2018
Prof. Dr. med. Annette Draeger
Abteilung Zellbiologie, Institut für Anatomie
3012 Bern (Schweiz)
- firstname.lastname@example.org. ch
Almost one century after the first administration of antibacterial compounds, bacterial pathogens continue to threaten human health. In the wake of growing antibiotic resistance, novel strategies are urgently needed for the prevention and treatment of bacterial infections. In contrast to antibiotics, which target processes that are essential for the survival of a bacterium, compounds that target virulence factors are less likely to lead to drug resistance. Recently, we have engineered liposomal decoys that efficiently sequestrate cytolytic toxins secreted by staphylococcal and streptococcal pathogens, including those secreted by methicillin-resistant Staphylococcus aureus. Deprived of their major virulence factors bacteria are cleared by the host immune system: injected intravenously, liposomes prevented the death of mice from fatal sepsis caused by Staphylococcus aureus or Streptococcus pneumoniae. Intranasal injection of liposomes protected mice from pneumococcal invasive pneumonia. Liposomes themselves are non-toxic for humans. Hence, their toxin-sequestrating properties can be exploited to combat severe bacterial infections, in particular those caused by antibiotic-resistant pathogens.
We will investigate the protective properties of engineered liposomes in order to develop formulations with broad therapeutic activity against the major Gram-positive human pathogen - with an emphasis on antibiotic-resistant bacteria. In addition, their efficacy against selected Gram-negative pathogens will be determined in view of further developing their therapeutic potential.
What is special about the project?
The development of antibiotic resistance is an unintended but unavoidable adverse event of every antibiotic treatment. Therefore, it is now opportune to consider another option: instead of directly killing the bacteria, it might be preferable to limit the damage they induce in individual host cells instead. Such a treatment relies on therapeutic assistance given to the epithelial and immune cells that represent the first line of defence against a pathogen attack but does not interfere with the pathogen itself, in order to avoid the emergence of drug-resistant strains. By leaving the eradication of microbes to the immune system, this concept also parts with the barely one century old belief that bacterial pathogens can be kept in check by antibiotics alone.
We have engineered liposomes, which neutralize bacterial toxins and are effective in the treatment of experimental infections by Gram-positive pathogens. At present, we are testing their efficacy against a wider range of bacterial virulence factors with the aim of increasing their therapeutic potential.
Henry BD, Neill DR, Becker KA ,Gore S, Bricio-Moreno L, Ziobro R, Edwards MJ, Mühlemann K, Steinmann J, Kleuser B, Japtok L, Luginbühl M, Wolfmeier H, Scherag A, Gulbins E, Kadioglu A, Draeger A, Babiychuk EB. Engineered liposomes sequester bacterial exotoxins and protect from severe invasive infections in mice. Nature Biotechnology 2015 doi:10.1038/nbt.3037
Persons involved in the project
Last update to this project presentation 03.07.2019