Objective
Disorder known as cystic fibrosis (CF). The life expectancy among CF patients is extremely low due to bacterial colonization of the airway epithelium and patients rarely attain the age of 40 years. The project objectives are: 1) To demonstrate the effectiveness of bacteriophages through in vitro experiments on cultured bacteria and airway epithelial cell cultures infected with these bacteria. 2) To prepare for the exploration of the possibilities and limitations of phage therapy for eradication of bacterial biofilms in the airways of heavily colonized patients, for which no other therapeutic outcome is still available. To achieve the key objectives the research activities will focus on the following: a) systematic bacteriology studies at a selection of European CF center(s); b) construction of a collection of genotypically characterized strains of S aureus and P. aeruginosa and a relative phage collection; c) screening of the selected phages against the clinical isolates; d) characterization of the candidate phages; e) construction of the complex phage preparation(s) ( "cocktails") with a broad host range; f) assessment of the efficacy of bacteriophage treatment with regards to the reduction of bacterial infection of airway epithelium cultured in vitro (cell culture model); g) Analysis of the obtained results Completion of the project will result in the following novel achievements: 1) Genotypical characterization of a collection of strains (at least 200 clinical isolates of S. aureus, P. aeruginosa and B. cepacia) obtained from CF patients as they occur in European CF center(s). 2) Screening of these pathogentic strains against the existing phage collections, together a minimum of 60 phage clones (if necessary new phage clones will be isolated as well); 3) Selection of at least 5-10 candidate phages specific to S. aureus, P. aeruginosa and B. cepacia for construction of phage "cocktail". Selection will be done on the base of the combination of their bactericidal potential, biological features and genetics. Investigation of their genetic structure underlies the objective of avoiding horizontal spread of bacterial genes (e.g. those encoding for imipenem drug resistance) as might be caused by some temperate phages. 4) Assessment of the effectiveness of bacteriophage application by studying growth reduction of phage-, antibiotic-, and their complex- treated bacteria in a airway epithelial cell culture model in comparison with phage- and antibiotic- untreated controls. These achievements will enrich the existing knowledge on the potential of phage therapy to improve the quality of life and prolong life expectancy of most CF patients. The project will contribute to Medical Biotechnology as well as to Clinical Microbiology. Where appropriate international patents will be filed to protect the groups IPR. Reports will be sent to INTAS each 12 month period and at the end of the project.
Topic(s)
Call for proposal
Data not availableFunding Scheme
NoE - Network of ExcellenceCoordinator
9000 Ghent
Belgium