Molecular mechanism of bacteriophage tail spike proteins in bacterial infection
At a glance
- Project leader : Dr. Sabina Gerber
- Co-project leader : Prof. Dr. Lars Fieseler
- Project team : Dr. Leandra Knecht, Angela Nauer
- Project budget : CHF 200'000
- Project status : completed
- Funding partner : Internal
- Contact person : Sabina Gerber
Description
Antibiotic resistance in pathogenic microorganisms is rapidly
increasing worldwide which urgently calls for novel agents and
innovative solutions for the treatment of bacterial infections.
Bacteriophages (phages) infect and inactivate bacteria in a highly
specific manner. Therefore, exploitation of phages represents a
highly promising alternative to antibiotics to detect, identify and
combat human bacterial pathogens. For potential applications in
medicine, high specificity of a phage for its bacterial host is a
tremendous advantage in order to avoid broad killing of commensal
human bacteria. However, the infection mechanism remains poorly
characterized to date which hampers development of phage-derived
solutions. Limitations in understanding the process on a
quantitative, molecular level is mainly due to lack of suitable
analytical methods.
Tail spike proteins (TSPs) are specialized hydrolytic phage
proteins located at the end of the phage tail, which govern the
first steps in bacterial infection by the phage. Initial events in
infection involve binding of the phage TSPs to the bacterial
surface followed by degradation of the bacterial polysaccharide
layer. We aim at understanding the molecular basis of these first
steps in infection through development of novel, quantitative
bioanalytical methods using TSPs produced in a phage-free context.
Elucidation of molecular details of the infection process is
crucial for understanding the mode of action and phage specificity
for further engineering of TSPs for broad, potential applications
in analytics and medicine. Methods developed shall be applicable
for other phage TSPs.
The project is performed in synergy with Prof. Dr. Lars Fieseler,
Head of Food Microbiology Research Group (ILGI) and Dr. Sabina
Gerber, Head of Bioanalytics Research Group (ICBT). Tackling the
questions specified is greatly strengthened by combined expertises
in microbiology, biochemistry and bioanalytics.