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Förslaget inkom 2003-01-07

PHAGE AS THERAPEUTIC AGENTS

OBS! ANSÖKNINGSTIDEN FÖR DETTA EXJOBB HAR LÖPT UT.
Because of increasing antibiotic resistance new methods are needed to treat serious infections. We aim to develop conditions where phage can be used for this purpose. Phage therapy has several advantages over antibiotics, for instance strict host specificity reducing adversal effects on the normal flora, but results have been somewhat inconsistent. Very successful results have been obtained in the former Soviet Union based on empirical experience, but next to nothing is known about properties of the phage that are important for success. All knowledge about phage-bacteria interaction comes from laboratory cultures, where bacteria display quite different properties than they do in our guts. Knowledge of gut interactions is essential to develop consistent therapy. Escherichia coli and phage T4 combine clinical relevance and well-developed genetics, making them a good model system for detailed investigation.

E. coli strains have been obtained from the bacteriological laboratory at the Uppsala Academic Hospital, isolated from patients with urinary tract infections and diarrhea, and tested with different T4-like phage, and recombinant phage constructed that have broad host range but most of their genomes from T4 to facilitate analysis.
The goal of the present project is to determine what phage properties are important for infection in liquid under different conditions relevant for the human gut. This will be done by analyzing mRNA differential display, and isolating and characterizing mutants able to kill bacteria more or less efficiently tha wild-type phage under the tested conditions.


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